To co-relate the use of hormonal contraceptives with positive Auditory and Vestibular alterations.medical history taking, audiometric test and vestibular test was applied to 60 women between the ages of 14 and 35 years old, and 30 of these women are on oral hormonal contraceptive consisting of Estrogen and Progesterone (risk group), for 6 months or more, that had no Auditory or Vestibular complaints prior to the usage of hormones; and 30 women that had never used these hormones (control group), with no Auditory or Vestibular complaints. Medical history was used to select the sample.Based on otoneurological findings, through quantitative research, we could see the prevailing Irritatative Peripheral Vestibular Syndrome and tinnitus in the risk group, without audiometric alterations.The use of oral contraceptives can provoke functional alterations in the inner ear, specially tinnitus and Irritative Peripheral Vestibular Syndrome in the risk group; but auditory threshold alterations were not evident. Women go through monthly reproductive cycles, which start during puberty and, usually, last during all their reproductive life, stopping at menopause. These cycles prepare the female reproductive tract for pregnancyA gonadotrophin release hormone (GnRH), synthesized by the hypothalamus, stimulates the release of two other hormones produced in the pituitary: follicle stimulating hormone (FSH), and the Luteinizing hormone (LH). The former stimulates the development of ovarian follicles and the production of estrogen by the follicular cells, the latter triggers ovulation (acts on the release of the secondary oocyte) stimulating the follicle cells and the corpus luteus to produce progesterone. Estrogen acts specially on the reproductive organs functioning and development regulation; and progesterone acts stimulating endometrial glands to secrete and prepare the endometrium for the blastocyst implantationWhen the oocyte is not fertilized, the corpus luteus starts to degenerate about 10 to 12 days after ovulation; estrogen and progesterone levels drop and the secretory endometrium enters its ischemic phase, and menstruation sets inCombined estrogen and progesterone pills (contraceptive pills), taken orally for a period of three weeks have anovulatory action, preventing fertilization from taking place. This occurs through gonadotrophin secretion inhibition by the pituitary acting on the hypothalamus. The progesterone agent present in the pill suppresses LH secretion and the estrogen agent is responsible for the FSH secretion suppression, showing a synergic effect. Besides, the estrogen component enhances the action of the progesterone agents, thus allowing a reduction on the doses of progesterone in the pill composition and, consequently, reducing its adverse effectsThe use of these contraceptive pills by women may cause different adverse reactions, such as: immune, metabolic, nutritional, psychiatric, vascular, ocular, gastrointestinal, hepatobiliary, skin, renal/urinary and auditory alterations; Central Nervous System disorders, and reproductive system disorders. Moreover, the body may trigger vertigo in the pre-menstrual syndrome or during the use of these hormones, due to estrogen and progesterone concentrationsTherefore, when vertigo and/or dizziness/hearing loss appear, it is necessary to investigate prior use of medication; it is necessary to know whether or not the symptoms started with the use of some substance or in changing a medication dosingPartial or total loss of auditory or vestibular function, during or after exposure to medications, solvents and other substances is called ototoxicity. Many are the potentially ototoxic substances, including cardiovascular drugs, central nervous system drugs, muscle relaxants, non-hormonal anti-inflammatory, antibiotics, hormones, respiratory tract drugs, antihistamines, contraceptive drugs, cytostatic drugs, anesthetics, appetite moderators, amongst othersBody balance depends on the integrity of the vestibular system, the somatosensorial system and vision. The labyrinth is responsible for the sense of balance and the body's position in space. Dizziness and vertigo set it when something interferes in the normal functioning of these systems.The biochemical integrity of the inner ear liquids is important for its proper functioning. The hormonal alterations caused by oral hormonal contraceptives may impair the homeostasis of labyrinth fluids, because they have direct influence over the enzymatic processes and on the action of neurtransmittersThere are some studies that correlate inner ear alterations with the action of hormones, which will be reported below.The use of oral contraceptives may lower hearing thresholds, without altering stapedial reflexThere are cases of sudden hearing loss because of the use of estrogen and progesterone, alone or in association. The prolonged use of these hormones may cause sensorineural hearing loss in the high frequencies, besides total or partial vestibular involvement. This is explained when we observe labyrinth irrigation, because the vascular obstruction of the internal auditory artery brings disorders to the territory it irrigates, involving the cochlea, vestibule or bothSome studies believe that otologic alterations  in women who use oral hormonal contraceptives may not be related to this therapy aloneIn a study carried out with women who used oral hormonal contraceptive pills, they observed that in relation to hearing capacity and self-perception, this use does not cause significant hearing alterations; however, it favors tinnitus symptoms. Notwithstanding, in another study, women who used oral contraceptives had significant and consistent hearing loss in some frequencies, when compared to normal menstrual cycle women who did not use the pillThis correlation between hearing alterations and the use of oral hormone contraceptives was observed in a case in which a young woman presented with sudden sensorineural hearing loss, preceded by tinnitus, and recovered after treatment. In this case, tinnitus should be considered a warning about the need to interrupt the hormonal therapyThere are research papers showing that oral contraceptives today have less estrogen and progesterone, being called “low dose pills”. The reduction on the doses of these hormones has significantly reduced sudden hearing loss in those patientsIn order to prove the influence of hormones in the body, normal pregnant women were submitted to vestibular assessment, showing greater sensitivity to mild vestibular stimuli, when compared to the control group , thus proving a labyrinth dysfunction during normal pregnancy, specially on the first quarter, probably secondary to the hormonal actionIn a study with albino guinea pigs, they studied the effective estrogen action on the hearing, manifested by an increase in brain stem auditory potential thresholds in 47% of the animals, thus confirming the ototoxicity potential of this hormoneAmong causes of vertigo, migraine is predominantly found among teenagers and adults. The use of oral contraceptives, intra-uterine devices or even hysterectomy, should be always considered in cases of recurrent chronic headaches, for there are indications that the use of a contraceptive method, specially hormonal, influence the occurrence of this disease. Among persons with migraine, 81% were female and 77% are between 16 and 50 yearsIn this study we shall approach the otoneurological alterations  accruing from the use of hormonal contraceptives by women for a minimum time period of 6 menstrual cycles. Our goal was to correlate the use of oral hormonal contraceptive use with possible hearing and vestibular alterations.The present study was carried out from the data about patient history, tonal/vocal audiometry and vestibular exam from 30 women who used the oral hormonal contraceptive method and in 30 women who did not use it (control group).In order to select the sample individuals, some criteria were used: females, aged between 14 and 35 years, minimum of 6 months on oral hormonal contraceptive with estrogen and progesterone, without hearing alterations complaints before starting to use hormonal contraceptive, and without using any other type of medication.To make up the control group, we selected women aged between 14 and 35 years, who did not use contraceptive hormones nor any other medication, with neither hearing nor vestibular complaints.Tonal threshold audiometry of all the patients were carried out in a sound proof booth, with the aid of an Amplaid A171 audiometer, calibrated according to the ANSI-69 standard, in 03/19/2003. We assessed the frequencies from 250Hz to 8000Hz (air) and 500Hz to 4000Hz (bone), according to the method used to determine the descending-ascending hearing thresholdThe results obtained from the audiometric tests were interpreted as to hearing level, according to the criteria used by Silman & Silverman, and as to the type of hearing loss Vestibular exams were carried out through the Contronic version 5 device. The tests used were: calibration, spontaneous nystagmus (eyes opened and eyes shut), semi-spontaneous nystagmus, positional nystagmus , pendular tracking, and post-caloric nystagmus (water at 44º and 30°) (attachment 3).After data collection, results were statistically treated. We build contingency tables (2 × 2) to describe the hearing and vestibular alterations frequence distribution between the two groups under comparison (risk and control groups). In order to check the significance of this association between the use of oral hormonal contraceptives with hearing and vestibular alterations we used the chi-squared test (c2) at a significance level of a = 0.005. Both the null and alternative hypothesis considered in these tests were, respectively, H0: there is no correlation between the use of oral hormonal contraceptives and hearing and vestibular alterations; and Ha: there is a relation between the use of oral hormonal contraceptive and hearing/vestibular alterations. Since we had a p value below the previously established level of significance a= 0.005), the null hypothesis was rejected (H0), thus showing a significant association between the use of oral hormonal contraceptives and hearing/vestibular alterations.Ethics: The present study was assessed and approved by the Ethics and Research committee of the Speech Therapy Specialization Clinic (CEFAC) under protocol # 133/04 and it was approved without risk and with the need for a Free and Clarified Informed Consent.In the control group, 100% of the sample (30 women) did not complain of hearing loss, tinnitus or dizziness. 70% (21 women) complained of sporadic headaches and 16.7% (5 women), complained of insomnia. In the risk group, 100% of the sample (30 women) did not complain of hearing loss; 33.3% (10 women) complained of tinnitus; 73.3% (22 women) complained of dizziness; 76.7% (23 women) reported sporadic headaches and 23.3% (7 women), insomnia. , Table 4In the audiometric test, 100% of the sample (60 women) had audiometric tests within the normal range, compared to 0% of altered audiometric test.In vestibular testing, the control group showed 23.3% of the sample (7 women) with irritative peripheral vestibular syndrome (IPVS) and 76.7% (23 women) had normal vestibular tests (NVT). In the risk group, 83.3% (25 women) had irritative peripheral vestibular syndrome (IPVS) and 16.7% (5 women) had normal vestibular tests (NVT). .Table 5VBased on the results of this research paper, we can see that hearing loss does not seem to be related to the use of oral hormonal contraceptives, since both the risk group and the control group did not show alterations in their audiometric tests, corroborating data from some previous research. Current contraceptive pills are mainly made up of low doses of estrogen and progesterone, thus reducing the occurrence of side effects, specially those related to the auditory function. Notwithstanding, the occurrence of tinnitus in the risk group was significant Results also point that headache and insomnia complaints may not be related to the use of contraceptive medication, because there was no difference between the number of women in the risk group and in the control group who had these symptoms .Notwithstanding, the headaches reported were identified as sporadic and not as chronic-recurrent (migraine). In some scientific findings, migraines are closely related to the use of hormonesThe use of oral hormonal contraceptive pills may have significantly influenced the complaint of dizziness (c2) = 34.737 and p value = 0.000), since this complaint was not seen in the control groupThe results of the vestibular tests show the relationship between irritative peripheral vestibular syndrome and the use of oral hormonal contraceptives, since 25 in 30 women of the risk group presented IPVS, while only 7 in 30 women of the control group had such alteration . This may be related to the influence of these hormones in the homeostasis of labyrinth fluidsWe then concluded that the use of oral hormonal contraceptives for a period of 6 months or more may cause functional alterations to the inner ear, specially tinnitus and dizziness, the latter is justified by the significant prevalence of irritative peripheral vestibular syndrome in the risk group, but did not show hearing threshold alterations.


The number of people with impaired hearing is increasing; knowing its magnitude is essential for public health.To study the prevalence and determinants of impaired hearing in Itajaí/SC.A population-based survey based on a World Health Organization protocol. Field research was carried out from July 2008 to 2011. Procedures for evaluating hearing in households: questionnaire, measurement of noise, otoscopy, pure tone audiometry at 1000, 2000, and 4000 Hz, tympanometry, and acoustic reflexes: individuals above 4 years; children under 4 years: evoked otoacoustic emissions (OAE), cocleo-palpebral reflex(CPR), tympanometry, and acoustic reflexes. In the elderly population a questionnaire of perception of hearing loss was applied.The study sample consisted of 379 individuals – 45.38% were males and 54.62% were females. Age-range: 11.34% up to 10 years; 64.39% 10 to 60 years, 24.27% over 60 years. Evaluation of the best hearing ear showed that 74.1% of residents had normal hearing, 18.9% had mild hearing loss, 5.1% had moderate hearing loss, 1.9% had severe hearing loss. Disabling impaired hearing was detected in 26 subjects: one child (otitis media); four adults ; 21 elderlies (presbyacusis). Of eight children under 4 years all presented CPR, three were normal examinations, two had absent OAE bilaterally, one had absent OAE in the right ear and one in the left ear.The prevalence of disabling impaired hearing in Itajaí was 7%; the highest prevalence was in the 50-year and above age group – the main cause was presbyacusis. Hearing is one of the essential senses for human communication; any abnormality in the hearing system at any stage in life may compromise the communication process.Studies in the 1990s have shown that about 70 million people worldwide have hearing loss over 55 decibels (dB)Although specific statistical data on hearing loss are sparse in Brazil, the Support Group for Universal Neonatal Hearing Screening  has published data on its website suggesting that the occurrence of hearing loss in neonates is 30 for every 10,000 live births in BrazilA review of several Brazilian epidemiologic studies on audiology that was published in 2011Several controversies remain about the incidence and prevalence of hearing loss. Definitions and criteria are still heterogeneous in research studies and demographic and epidemiologic data on hearing loss in Brazil remain scarce.Because of the geographical extent of Brazil and population differences among regions, further studies using a common methodology are needed.At present two Brazilian population studies using a method proposed by the WHO have been conducted. Béria et al.The main etiologic factors of hearing loss in infancy were genetic and neonatal causes, such as premature birth, low birth-weight, anoxia, hyperbilirubinemia, ototoxic drugs, sequelae and/or complications of diseases . The most common causes in adults are presbycusis, followed by noise-induced hearing lossBecause the majority of hearing losses can be avoided, or preventive measures can minimize the difficulties that result from hearing loss, an early diagnosis and intervention, as well as knowledge about the magnitude of hearing, are paramount.Therefore, the main purpose of this study was to investigate the prevalence of hearing loss and its determinants in the city of Itajaí, SC, by applying a population-based study according to a WHO protocol to generate a standardized database containing epidemiologic information about hearing loss in Brazil.The institutional review board of Vale do Itajai University (UNIVALI) approved this study (no. 153/2008).The population of Itajaí is 183,373 people ; it contained information about the objectives, benefits, and risks of the study.Visits were made to 774 households, 684 of which were privately-owned houses, 10 were collective households, and 80 were non-residential houses. Evaluations were made of 715 people; however, 336 were excluded by being part of incomplete households according to the population base research method, as suggested in WHO inclusion criteria. Thus, the sample consisted of 379 people from complete households who were evaluated; the loss was 10% of the ideal calculated sample .Hearing Handicap Inventory for the Elderly, Screening Version, HHIE-Shandicap;11% to 22% meant mild to moderate perception of handicap, and over 22% meant significant or severe perception of handicap.The following procedures, based on a prevalence assessment protocol recommended by the WHO (1999), were applied: a questionnaire, measurement of environmental noise levels, meatoscopy/otoscopy, and investigation of auditory thresholds at 1000, 2000, and 4000 Hz. Transient evoked otoacoustic emissions and a behavioral audiological assessment were made of children aged 0 to 4 years. Additionally, automatic tympanometry and investigation of ipsilateral acoustic reflexes were carried out in all subjects. A questionnaire based on a translation of the The first procedure was to apply a general questionnaire to gather identification data, age, gender, education level, and work of household dwellers that were chosen for this study; this was a tactic for generating interaction with the families.Sound Meter 840029) was used to measure the ambient noise level to make sure that ambient noise did not exceed 40 dBH; hearing assessments were not made in acoustic booths . The sound pressure level meter was kept on throughout the procedures.A digital sound pressure level meter  and by testing the cochleo-palpebral reflex (CPR) with an agogo.Otoport device was used for investigating transient stimulus evoked otoacoustic emissions (TOAE); the child was seated in their mother's lap. Tested frequencies were 1000, 1500, 2000, 3000, and 4000 Hz; the pass-fail criterion was the presence of TOAE in at least three frequency bands.An Handtymp device was used for automatic tympanometry and testing of ipsilateral acoustic reflexes. Because it is a quick, objective, non-invasive procedure that does not require behavioral responses from subjects, it was applied to all age groups, including children aged below 4 years.A Mean auditory thresholds at 1000, 2000, and 4000 Hz for the best ear were used to assess the degree of hearing loss. The following parameters were applied for children aged up to 15 years: 0–15 dB – normal; 16–30 dB – mild hearing loss; 31–60 dB – moderate hearing loss; 61–80 dB – severe hearing loss; and over 81 dB – profound hearing loss. The parameters for adults were: 0–25 dB – normal; 26–40 dB – mild hearing loss; 41–60 dB – moderate hearing loss; 61–80 dB – severe hearing loss; and over 81 dB – profound hearing loss.Incapacitating hearing loss was defined as the presence of auditory thresholds equal to 41 dB or more in adults, and 31 dB or more in children below 15 years of age. The WHO definition of incapacitating hearing loss considers only permanent hearing loss as incapacitating. In our study, as in Béria et al.sIndividuals with any abnormality in our evaluations were referred to the ‘Hearing Health Care Unit' of Vale do Itajai University (UNIVALI) for complete otorhinolaryngologic and audiology assessments if needed. Subjects were given a card with the date and time of the visit, and the reasons for this visit were explained.For quality control telephone contact was made with the dwellers of 10% of participating households to ask about their relationship with interviewers and if all the expected procedures were carried out.The statistical study consisted of simple and relative frequency distribution analysis, crossing the data to study the variables sex, age group, and hearing level in the best ear. The variables age and sex were compared with the IBGE (2011) population based study to check the representativeness of the sample. Data are presented as frequencies and percentages , and as means and standard deviations (quantitative variables).According to IBGE (2011) census data, there were 64,679 households in Itajaí. Of these, 57,815 (89.4%) were classified as private occupied households, 57,612 (89%) with census interviews and 203 (0.4%) without census interviews, 6,801 (10.5%) were private unoccupied households, and 63 (0.1%) were classified as collective households; the mean number of dwellers per household was 3,16. For this study 774 households were visited, 684 (88.37%) of which were private, as follows: 300 (38.76%) occupied (137 complete households (17.70%) and 163 (21.05%) incomplete), 384 households were not occupied, (256 (33.07%) were closed, 128 (16.54%) were vacant); 10 (1.30%) were collective households, and 80 (10.33%) were non-residential buildings. The mean number of visited dwellers per household without incapacitating hearing loss was 2.8; this mean was 2.54 for households with at least one persons presenting incapacitating hearing loss.The distribution by census sectors showed that there were no significant differences when considering the number of complete households and the prevalence of hearing loss per sector. Mild hearing loss was found in all of the 14 census sectors that were evaluated; moderate hearing loss was found in 10 of these sectors, and severe hearing loss was encountered in six sectors.Of the 379 inhabitants of Itajaí that comprised the study sample, 172 (45.38%) were male and 207 (54.62%) were female.An analysis of the minimum hearing level in the best ear showed that 74.1% of subjects were normal-hearing, and 25.9% had some degree of hearing loss . Thus, the prevalence of incapacitating hearing loss was 7% .Figure 3The mean noise in 137 complete households that were studied was 38.4 dB; the median was 38.3 dB, the minimum was 32.2 dB, and the maximum was 51.9 dB (standard deviation – 3.5). These numbers did not correlate with the presence or absence of hearing loss.Tympanometry revealed a predominance of the type A curve (93.4% in the left ear and 93.1% in the right ear); there was a lower incidence of the type B curve (5.8% in the left ear and 5.3% in the right ear) e C (0.8% in the left ear and 1.7% in the right ear). All were conduction hearing loss cases. Similarly, acoustic reflexes were found in most of the study population. Considering all degrees of hearing loss, the type A curve and reflexes were the most frequent.Relating personal and family health history and the presence of hearing/otologic complaints to incapacitating hearing loss – detected in 26 subjects of the sample – nine had no complaints, and the other 17 subjects had a positive history and hearing/otologic complaints, of which seven had associated symptoms (two manifested vertigo and five had tinnitus). Co-morbidities included diabetes mellitus (2 cases), systemic elevated arterial blood pressure (2 cases), a history of stroke (2 cases), and one subject had undergone chemotherapy. Of these 26 cases, one was a child ; four were adults aged over 45 years . Among 21 elderly subjects with presbyacusis, 17 perceived their hearing loss  and four had no perception of hearing loss. The HHIE-S of all 92 sample subjects concluded that 71 elderly subjects were classified as not having incapacitating hearing loss, of which 39 had no perception of hearing loss, 18 had mild to moderate perception, and 14 had severe perception. Of 21 elderly subjects with incapacitating hearing loss, one used a hearing aid bilaterally and was a patient of Practice Vale do Itajai University (UNIVALI), two refused to continue treatment, and 18 were referred for fitting of hearing aids. At present hearing aids have been fitted on 16 patients, and are being selected for two other patients. Considering all degree of hearing loss and including the hearing level of the worse ear, besides the 26 subjects with incapacitating hearing loss, another 109 subjects also had abnormal tests. For all 315 cases, the most frequent etiologies were: presbyacusis (40.74%), idiopathic (17.04%), ear wax (6.66%), chronic otitis media (5.92%), otosclerosis (3.70%), noise-induced hearing loss (2.22%), labyrinthic disease (1.48%), papilloma of the outer ear canal (0.74%), and associated causes (21.5%) see . Of 109 This is the third study on a population survey about the prevalence of hearing loss after Béria et al.'sThe study sample consisted of male and female subjects, allocated to age groups ranging from less than 4 years to 80 years or more. The total sample comprised 379 evaluated subjects in 137 complete households, residents of 14 census sectors in Itajaí. The IBGE census data were applied to characterize and analyze the representativeness of households and groups of individuals; discrepancies were due to the fact that the IBGE employs more teams, interviewees are required to respond, t interviewers do not enter the households, that dwellers are not required to be in the house, and that the time taken for interviews is shorter. In our study, household dwellers had to agree and all had to be present in the house; it was also necessary to enter the households to carry out clinical interviews, which required more time. The most significant variations between the study sample and the IBGE census were found in the 0–4, the 20–30, and the 60+ age groups in both sexes and in the 40–50 years group in females. A smaller proportion of children aged up to 4 years, of subjects aged 20–30 years and 40–50 years in our sample is probably due to young children staying in crèches and nurseries and adults at work; older people predominated in the sample, reflecting the fact that this age groups stays more at home.Visitation was made of 774 households, in which 715 people were evaluated; as the WHO criteria were followed strictly, these numbers were reduced to 137 complete households and 379 subjects in the sample. The most significant difficulties were due to the field survey. Although a letter was sent to the houses that were chosen to provide information about the project and letting the household dwellers know that a visit would be made by an Auditory Health team – a strategy that minimized refusal – many houses could not be included because the head of the family refused to participate. Another difficulty were the floods, which affected about 90% of the town in the second semesters of 2008 and 2009; this often made it impossible for the team to visit houses. Households in which all dwellers could not be evaluated were excluded from the sample; this was due to refusal to participate, absence in up to three visits, or rains and floods that resulted in destruction of houses and removal of household dwellers with subsequent loss of contact.Most of the sample subjects were normal hearing, followed by cases with mild hearing loss (18.9%), as also noted by Béria et al.The distribution of hearing loss per census sectors revealed no predominance of incapacitating hearing loss in specific census sectors.The mean intensity of household noise and the number of dwellers per household did not influence the presence or not of incapacitating hearing loss.The prevalence of incapacitating hearing loss in Itajaí was 7%; this is similar to the value Béria et al.Most cases of incapacitating hearing loss were found in individuals aged over 50 years; it predominated in individuals aged over 70 years. This results is similar to that published by Béria et al.The personal health history and the auditory complaints showed that 282 of 345 subjects without incapacitating hearing loss had no complaints; however, 63 subjects without incapacitating hearing loss did have complaints about hearing. Of 26 sample subjects that had incapacitating hearing loss, 17 had complaints and nine were complaint-free. The HHIE-S of 92 elderly subjects in the ample showed that 39 of 71 elderly individuals classified as not having incapacitating hearing loss had no perception of hearing loss; 18 had mild to moderate perception, and 14 had severe perception. In the group of 21 elderly subjects with incapacitating hearing loss, 17 had perception of hearing loss, three had a HHIE-S showing mild to moderate perception, 14 had severe perception, and four did not have any perception of loss. Auditory complaints and/or perception of hearing loss may be – in the study sample – considered indicative factors of the presence of incapacitating hearing loss.Even in cases not classified as incapacitating , many subjects also had complaints and perception of incapacity, showing the negative impact of hearing loss, irrespective of its degree, on the quality of life of individuals with hearing problems.Another interesting result in our study was that when all detected abnormalities and the levels of the worse ear were taken into account, 109 subjects (28.76%) presented abnormalities, of which about half (55 cases – 50.46%) were solved by medical and/or surgical therapy, and another half (54 cases – 49.54%) were asked to return for follow-up of their auditory or otologic condition. Of the 26 incapacitating cases of hearing loss, 24 (92.31%) have already been or are being rehabilitated; one individual already used a hearing aid, was a patient of the ‘Hearing Health Care Unit' and a member of the municipality, one patient successfully underwent otorhinolaryngologic surgery, and two refused to return for follow-up.The most frequent etiologies of hearing loss among the population with incapacitating hearing loss in our sample were: presbyacusis(80.76%), chronic otitis media (7.69%), idiopathic conditions (7.69%), and noise-induced hearing loss (3.84%); thus, 11.53% were potentially avoidable.These data underline the importance of early detection and treatment of hearing loss, as most may be resolved or improved with therapy.The prevalence of incapacitating hearing loss  in Itajaí was 7%; it predominated in individuals aged over 50 years, and the main cause was presbyacusis.At the same time, it was clear that by detecting hearing problems in this specific population, treatments and procedures were undertaken that solved and/or minimized the hearing losses that were encountered.It is hoped that this study may contribute to developing a database with information about hearing in Itajaí, and that in future this initiative may be extended to other municipalities in the state of Santa Catarina. This database may guide measures, minimize costs, optimizing and directing funds for the best use in assessing, diagnosing, and rehabilitating individuals with hearing loss.


Access to low-frequency acoustic information in cochlear implant patients leads to better speech understanding in noise. Electrocochleography (ECochG) can provide real-time feedback about the health of the cochlea during the insertion process with the potential to reduce insertion trauma. We describe our experiences of using this technique. Data from 47 adult subjects with measurable residual hearing and an Advanced Bionics  SlimJ (46) or MidScala (1) electrode array were analyzed. ECochGs were recorded intraoperatively via the implant. The surgeon adjusted the course of the electrode insertion based on drops in the ECochG. The final array position was assessed using postoperative imaging and pure tone thresholds were measured before and after surgery. Three different patterns of ECochG response amplitude were observed: Growth, Fluctuating and Total Loss. Subjects in the growth group showed the smallest postoperative hearing loss. However, the group with fluctuating amplitudes showed no meaningful correlation between the ECochG responses and the postoperative hearing loss, indicating that amplitude alone is insufficient for detecting damage. Considering the phase of the signal additionally to the amplitude and reclassifying the data by both the phase and amplitude of the response into three groups Type I–Type III produced statistically significant correlations between postoperative hearing loss and the grouping based on amplitude and phase respectively. We showed significantly better hearing preservation for Type I (no drop in amplitude) and Type II (drop with a concurrent phase shift), while Type III (drop without concurrent phase shift) had more surgery induced hearing loss. ECochG potentials measured through the implant could provide valuable feedback during the electrode insertion. Both the amplitude and phase of the ECochG response are important to consider. More data needs to be evaluated to better understand the impact of the different signal components to design an automated system to alert the surgeon ahead of damaging the cochlea. The preservation of any low frequency residual hearing in patients who undergo cochlear implant surgery has become an important consideration in electrode array design and surgical technique. Low-frequency hearing is associated with improved hearing performance, especially in difficult listening environments . Access to low-frequency acoustic information in cochlear implant patients can enhance the segregation of competing voices, which leads to better speech understanding in noise, and the benefit of Electric Acoustic Stimulation (EAS) has been shown in numerous studies, e.g. –4. HowevElectrocochleography is the process of recording electrical potentials generated in the cochlea and from the auditory nerve in response to an acoustic stimulus. It consists of four waveforms which can be separated using filtering and the appropriate time window. The cochlear microphonic (CM) is an alternating current voltage that reflects the instantaneous displacement of the basilar membrane and comes from active movements from the outer hair cells . SummatiThe first cochlear potentials were recorded from cats by Wever and Bray in 1930 but not successfully recorded in humans until 1960 , 14. TodFurther research was undertaken to establish if the observed variations in ECochG responses could be related to postoperative residual hearing or even speech perception outcomes –26. CampConversely, a number of studies have shown no relationship between intraoperative ECochG responses and thresholds , 30, 31.We started using ECochG in 2016 to systematically collect inner ear potentials during the electrode insertion process in as many subjects as possible who had measurable residual acoustic hearing. These potentials were then related to the pre- and postoperative hearing thresholds and the final position of the electrode array of these subjects. The main objective of this study was to describe our experiences of using this technique in a large sample of Advanced Bionics  CI recipients with some measurable hearing in the implanted ear.ECochG was used as a tool to guide the surgeon during the insertion of the CI array. Sharp drops in the ECochG responses were communicated to the surgeon, who adjusted the course of the electrode array, aiming to restore the amplitude of the continuously measured intracochlear potentials. The final position of the electrode array was assessed using postoperative image analysis and pure tone thresholds were recorded before and after surgery. Further analysis was performed to look for any features of the ECochG response that could possibly indicate a greater loss of residual hearing post-surgery. The hypothesis was that by using this technique the insertion process could be managed with less trauma and subsequently result in better preservation of residual acoustic hearing.64 subjects aged 18 and above were included in the study. These were patients who had opted for an Advanced Bionics  cochlear implant and had measurable residual hearing (HL < = 80dB) for at least one frequency. All subjects who fulfilled those inclusion criteria were asked to participate in the study one or two days before the surgery.Subjects followed routine surgery and follow up procedures. Additional to the routine measurements, ECochGs were recorded intraoperatively via the implant. For the following analyses, 17 of the 64 subjects were excluded as their intracochlear potentials were measured with the much slower 1st generation ECochG system which is not capable of providing real-time feedback. So, data from 47 (numbers 18–64) subjects are presented in this paper.One subject had a MidScala electrode array and all others received a SlimJ electrode array. Age at implant ranged from 19.5 years to 84.8 years with a mean of 56.9 years. Two hearing losses were acute, six unknown and four had a hearing loss since childhood. The remaining 35 subjects had a progressive hearing loss. Most hearing losses were of unknown cause (25), six losses were hereditary, and seven patients experienced sudden hearing loss. Other etiologies for individuals were Cogans syndrome, Ushers syndrome, noise exposure, sepsis, measles, mumps, trauma, legionella disease and oxygen deficiency. Duration of hearing loss prior to implantation ranged from 1.7 to 50.3 years with a mean duration of 22.1 years.The study was approved by the ethics board of the Medical University Hannover with Nr 2867–2015 and was conducted in accordance with the principals laid out in the Declaration of Helsinki. All subjects signed an informed consent for participation and to enable their data to be included in this study.Pure tone thresholds for 125, 250, 500, 1000, 1500, 2000, 4000 Hz were measured under headphones using calibrated clinical equipment. This was done prior and 4–6 weeks after surgery at the first fitting of the speech processor.Intracochlear ECochG recordings were conducted through an Advanced Bionics HiRes90K or Ultra CI system . Advanced Bionics research ECochG software running on a laptop was used for stimulus generation and data collection. The laptop was connected to the CI through the Clinical Programming Interface 3 (CPI3) and the NaidaCI Q70 speech processor. The amplifier in the implant was configured to have a gain of 1000. The sampling rate was 9,280 Hz. The low pass filter was set at 5,000 Hz. The most apical contact of the HiFocus Mid-Scala and SlimJ electrode arrays was used as the recording electrode, the case as reference electrode.The acoustic stimulus was generated by a Behringer soundcard and presented through a sterilized ER-3A insert earphones . As acoustic stimulus, a 53 ms long sinusoidal tone burst at 500 Hz with a level of approximately 110 dB SPL was used. The CPI3 received an external trigger by the soundcard to synchronize stimulus generation and ECochG recording through the CI. Consecutive buffers were presented with alternating polarity and the cochlear microphonic (CM) were computed by subtraction of the two recordings. The recordings were acquired continuously during insertion of the CI electrode and averaged until a signal to noise ratio of 12 dB was reached or a maximum number of 40 averages reached (with significant responses resulting in up to 8 measurements per second). The CM is transformed to the frequency domain with a FFT (Fast Fourier Transform). The response magnitude is derived from the FFT bin containing the stimulus frequency. The noise floor is estimated by taking the mean of a few surrounding bins.The cochlea was approached using a standard posterior tympanotomy and the round window was opened for manual insertion of the electrode array by making a slit through the round window membrane. The electrode array was inserted slowly over 1–2 minutes as it is our standard clinical practice in hearing preservation surgeries. ECochG responses were measured continuously during the insertion and the surgeon was informed verbally about any changes. There was no strict procedure how to react to changing ECochG amplitudes, but generally the surgeons behaved as follows:When the amplitude dropped during advancing the electrode array, the insertion was paused, or the array was pulled back slightly.When the response recovered completely or partially, the surgeon continued to insert the array, maybe with a different angle or more carefully than before.When the amplitude dropped again during insertion and only 1–3 contacts were outside the cochlea, the electrode array was pulled back again for amplitude recovery and left in place at that position.If the amplitude drop occurred with 13 or less contacts in the cochlea and restoring the ECochG amplitude was not possible, full insertion was performed anyway.Advanced image processing was conducted for estimating the angular insertion depth and scalar location of the electrode. The angular insertion depth was calculated in a coronal plain projection with a 0° reference line projected through the middle of round window and the centre of the modiolus . AnotherFor the assessment of the scalar location of the electrode array, two different methods conducted by two independent experts were applied: The first observer applied the image fusion (co-registration) technique of preoperative MRI and postoperative CT scans as described by Dees et al. (2016) and Dietz et al. (2016) , 36. TheIn 40 out of 47 subjects Cochlear Microphonics above the noise floor could be measured successfully. The intra-OP monitoring results show a large variability over all subjects . For exaIn 46 cases (ID 63 was not available), post-operative CT scans and preoperative MRI images were available. The insertion angle, the distance of the blue marker to the round window and potential translocations were analyzed. In The mean insertion angle was 375°  which is a little less than the 400–420° which is usually reported for the SlimJ. In 38 subjects the blue marker was 1 mm or more outside the round window, and in 13 subjects it was 3 mm or more.There was only one clear translocation with the MidScala electrode (ID 27) at around 100° from scala tympani to scala vestibuli. The ECochG response dropped during the last part of the insertion from 25μV to 8μV but was still measurable.There were four additional subjects where the image analysis indicated potential contact to the basilar membrane . In subject ID 31 no responses at all could be measured but in the other two, the amplitude dropped to noise floor during the insertion but recovered and was measurable at the end .In some cases, the most apical electrode contact, which is used to measure the potentials, reaches or even passes the characteristic frequency (CF) of the stimulation frequency, usually 500 Hz. In those cases, a drop in amplitude could be caused by the increasing distance to the signal generator. Sometimes the electrode array was inserted and pulled back a little because of a drop in CM amplitude. So regarding the postoperative CBCT analyses, we can only report on the final insertion depth—not the maximum insertion depth theoretically reached during surgery.In two implantations (ID 24 and ID 28) the final position corresponded to a CF smaller than 500 Hz (448 Hz and 489 Hz respectively). No loss in CM amplitude was observed for ID 24. In ID 28 a drop in amplitude was observed and this was accompanied by a large post-operative hearing loss.In four implantations  the final position corresponded to a CF between 500 Hz and 600 Hz . As these values are only estimations based on Stakhovskaya , this woResidual hearing was measured 4 weeks and 4 months after surgery. As the audiograms from the 4 months appointment were missing for 6 subjects, we decided to only evaluate the 4-week data. In However, we mainly observed three different patterns: Growth (with no large drops during the insertion), Fluctuating (where some larger drops were observed but by the end of the insertion the response was still present) and Total Loss (where a response could be measured during insertion but not at the end).To categorize the insertion patterns objectively, we set up some arbitrary threshold values based on the maximum amplitude measured during insertion (max), the minimal amplitude following max (min) and the end amplitude when insertion and coiling is finished (end) . Weder eThe LF PTA HL for the subjects in each group are shown in Also we computed the correlations between several variables, but no significant relationships were observed see .Koka et al. (2018) and Giardina et al. (2019) both showed that the phase information of the response might contain useful information , 29. A C◦ Type I: no drop > 5 dB◦ Type II: drop > 5 dB with concurrent phase shift◦ Type III: drop > 5 dB without concurrent phase shiftTo ensure that the worse hearing preservation in the Type III group was not an effect of preoperative residual hearing, the pre-operative hearing thresholds for the three groups were compared. There were no significant differences .Our findings show the feasibility of measuring ECochG potentials through a cochlear implant device from inside the cochlea. Responses were recorded from 85% of the subjects. Missing responses in the other seven subjects could be attributed to poor residual hearing, bad acoustic coupling of the speaker in the outer ear canal, fluid in the middle ear, kinking of the sound tube or high impedance of the ground electrode used for recording the responses (the case electrode). Making measurements through the implant electronics instead of using external measurement equipment required little additional hardware and the setup in the operating theater was comparatively simple. This allows for its widespread use as a routine clinical tool. ECochG responses recorded from inside the cochlea are significantly larger than externally measured potentials and this compensates for the lower resolution of the integrated amplifier of the implant electronics compared to an external electrodiagnostic system . The easIt is important to consider that the study was not purely observational. By reacting to the amplitude changes during insertion to attempt to avoid cochlear trauma, a simple correlation of the intraoperatively measured amplitudes and the hearing preservation cannot easily be made. Research has also shown, that even in purely observational trials ECochG amplitude could fluctuate , 38. ButFrom looking at the ECochG amplitude alone, we can conclude that the subjects with a more or less constant increase in the potentials during the insertion process (group “growth”) showed the smallest loss of their acoustic hearing pre- vs. postoperatively. This is also in line with previous work by Campbell and colleagues . HoweverAmplitude changes during the insertion could result from the change of the recording site in relation to the generator as well as from cochlear trauma. It is therefore necessary to consider more parameters than just the amplitude of the CM. Koka et al. (2018) first described a method to take the relation of the phase between the acoustic stimulus and the recorded signal into account . The ideIt needs to be considered though that in our subjects the intracochlear region with a CF equal to the stimulus frequency was hardly reached, although Bester et al.  have shoThe partial insertion in cases of a recovering CM response, where only 1–3 electrode contacts have been left outside the cochlea, is motivated by the increasing chance of cochlear trauma with insertion depth . In caseTaking both the phase and the amplitude into account allows for a discrimination between two scenarios: (1) the ECochG amplitude drops because the basilar membrane is being touched or even damaged or (2) the ECochG amplitude drops because the generator has just been passed and damage is unlikely. Grouping our data according to this extended notion gave us far better stratification and resulted in a statistically significant difference in post-operative surgery-induced hearing loss between the groups. We do not claim to have the perfect analysis method or can explain everything which happens during and (maybe more importantly) after the surgery to the inner ear. However, considering not only the amplitude of the CM response but also the phase information, seems to reveal important information which needs to be considered in the interpretation of the results. Future research should continue to focus on this approach to optimize the usefulness of ECochG in preventing intraoperative cochlear damage during electrode insertion.ECochG potentials measured through the CI electrode array can give valuable feedback to the surgeon to determine when trauma is possibly impending. Both the amplitude and phase of the EochG response are important to consider. More data needs to be evaluated to better understand the impact of the different signal components to design an automated system to alert the surgeon ahead of damaging the cochlea.S1 Data(XLSX)Click here for additional data file.


Hearing loss, frequently with tinnitus, is the main symptom of acoustic neuromas (ANs), which compress the cochlear nerve and affect the cochlear blood supply. This vascular mechanism explains why atypical, fluctuating deafness, with audiometric features of retrocochlear involvement, may occur in this condition.An early diagnosis of ANs is essential for a good prognosis. Physicians should recognize the clinical signs of neurinomas, particularly in individuals aged just over 40 years; this is true even in cases of symmetrical sensorineural hearing loss.The brainstem auditory evoked potential (BAEP) is an objective, non-invasive method for a neurophysiological analysis of auditory pathways from the inner ear to the high brainstem. It is a short latency potential that generates a wave series (from I to VII) that appears within the first 10 ms after a sound stimulus is presented. These waves are generated due to the sequential activation of auditory pathway structures, and are picked up by electrodes placed on the skin.A male Brazilian patient aged 74 years, born in Itatiba, was referred to the ENT outpatient unit from another town for the hearing aid program. He complained of decreased hearing in the left ear. The patient complained of dysacusis and ear fullness in the left ear for the past 2 years; there was no dizziness or tinnitus. Pure tone audiometry showed mild downward sloping sensorineural dysacusis in the left ear, and decreased hearing over 2 KHz in the right ear . The speA second audiometry one year later revealed severe flat sensorineural dysacusis in the left ear, and mild sloping sensorineural hearing loss in the right ear ; the speDuring the 1980s, MRI started to be used in the diagnosis of small lesions (its sensitivity for small tumors is 100%According to some authors, the sensitivity of BAEP varies with the tumor size; it is, therefore, a less reliable method. Dornhoffer et al. reported a 93% sensitivity for tumors measuring less than 1 cm.The advantage of BAEP is its lower cost; it may be done first to reduce the number of patients requiring MRI. If retrocochlear disease is suspected, MRI may be done even if the BAEP is normal, given its sensitivity range according to the tumor size.This paper aimed to demonstrate the need and importance of a complete audiological evaluation in all cases of bilateral sensorineural dysacusis with minor asymmetry.


PTPRQ gene, encoding protein tyrosine phosphatase receptor Q, plays an important role in maintaining the stereocilia structure and function of hair cells. Mutations in the PTPRQ gene have been reported to cause hereditary sensorineural hearing loss. By using next-generation sequencing and Sanger sequencing, we identified a novel compound heterozygous mutation (c.997 G > A and c.6603-3 T > G) of the PTPRQ gene in a Chinese consanguineous family. This is the first report linking these two mutations to recessive hereditary sensorineural hearing loss. These findings contribute to the understanding of the relationship between genotype and hearing phenotype of PTPRQ-related hearing loss, which may be helpful to clinical management and genetic counseling.Hearing loss is among the most common congenital sensory impairments. Genetic causes account for more than 50% of the cases of congenital hearing loss. The  It is ePTPRQ gene, located in the DFNB84 region of chromosome 12q21.31, is comprised of 58 exons , shortened stereocilia in outer hair cells (OHCs), and loss of hair bundles in both OHCs and IHCs were observed . Computed tomography (CT) and magnetic resonance imaging (MRI) of the temporal bone showed no abnormal malformations. Parents reported no history of miscarriage or stillbirth. The physical examination, otoscopy, and medical history were performed at the outpatient clinic of Wuhan Union Medical College Hospital.https://www.ncbi.nlm.nih.gov/nuccore/), the Database of Single Nucleotide Polymorphisms (dbSNP) (http://www.ncbi.nlm.nih.gov/projects/SNP/), and the 1000 Genomes Database . According to the sequencing results of two probands, Sanger sequencing was performed to confirm whether their parents had the same mutations. Using online tools such as HSF (http://www.umd.be/HSF3/HSF.shtml), FF (http://www.fruitfly.org/seq_tools/splice.html), SpliceAI (https://spliceailookup.broadinstitute.org/), an assessment was made to determine whether mutations occurring in the introns affected hnRNA splicing.The method has been described in detail in our previous articles . BrieflyBoth patients failed the newborn hearing screening and were diagnosed with congenital sensorineural hearing loss. The ASSR of Proband II-1 showed the thresholds of the left ear were 30, 35, 55, 65, 65, and 70 dBnHL at 0.25, 0.5, 1, 2, 4, and 8 kHz, while the thresholds of the right ear were 30, 45, 70, 65, 70, and 70 dBnHL at 0.25, 0.5, 1, 2, 4, and 8 kHz . The ASSPTPRQ: c.997 G > A and c.6603-3 T > G. The mutation c.997 G > A occurred in EX7/CDS7 in the PTPRQ gene, causing the substitution of no. 997 nucleotide from guanine to adenine . Both probands carried compound heterozygous mutations of  adenine . The mut adenine . The pro adenine . The mutPTPRQ hnRNA splicing using the online bioinformatics database. All three database tools, HSF(http://www.umd.be/HSF3/HSF.shtml), FF(http://www.fruitfly.org/seq_tools/splice.html), and SpliceAI (https://spliceailookup.broadinstitute.org/), suggest that mutations c.6603-3 T > G will change the original acceptor site and hnRNA splicing. However, patients did not intend to participate in the minigene splicing assay. Therefore, we did not verify the effect of mutation c.6603-3 T > G in in vitro experiments.The PTPRQ protein is composed of three types of domains, namely, 18 fibronectin III repeats domain (FN III domain), transmembrane domain, and tyrosine–protein phosphatase domain (PTPase domain). The mutation c.997 G > A causes the original TGG at nucleotide nos. 976–978 to become TAG, which corresponds to the termination codon . The mutPTPRQ in the family, as the probable cause of sensorineural hearing loss.Both probands failed the newborn hearing screening and were diagnosed with congenital sensorineural hearing loss. The proband’s parents were consanguineous. However, they did not provide more detailed information on family members. By using an approach of next-generation sequencing and the Sanger sequencing method, we identified c.997 G > A and c.6603-3 T > G of PTPRQ causes termination of protein synthesis. The mutant protein contains only one complete fibronectin III domain, the other domains are completely deleted , mutation c.6603-3 T > G of PTPRQ may cause altered hnRNA splicing, which can lead to changes in the composition and function of the PTPase domains. Neither mutant protein in two probands lacks the PTPase domains that are critical for the normal functioning of the PTPRQ protein. The PTPase domains have phosphatidylinositol phosphatase activity, so the PTPRQ protein can regulate the local phosphoinositides' concentration in a specific area. Furthermore, phosphoinositides play a role in cell growth, polarity, and movement by regulating the reorganization of actin filaments  in a Chinese family with non-syndromic sensorineural hearing loss. Our study expanded the spectrum of PTPRQ mutations. These findings contribute to the understanding of the relationship between genotype and hearing phenotype of PTPRQ-related hearing loss, which may be helpful to clinical management and genetic counseling.We identified a novel compound heterozygous mutation of


Although telomere length has a significant relationship with various age-related diseases, studies on its relationship with hearing status in adults are limited and equivocal. This study investigated the associations between mean telomere length (MTL) and low-, speech-, and high-frequency hearing threshold shifts of adults in the United States.A total of 2,027 adults, aged 20-69 years, from the National Health and Nutrition Examination Surveys  were included in the analytic sample. The quantitative polymerase chain reaction method was used for the MTL assay, and MTL was expressed using the telomere-to-single copy gene (T/S) ratio. Hearing loss was defined as a pure-tone average (PTA) for the better ear at ≥ 20 dB HL at frequencies 500, 1,000, 2,000, and 4,000 Hz. Univariate and multivariate linear regression analyses and smooth curve fittings were conducted to evaluate the correlation between MTL and low-, speech-, and high-frequency hearing levels.P = 0.008). When the T/S ratio exceeded0.82, MTL was not associated with high-frequency PTA .The mean age of the participants was 40.60 ± 12.76 years, including 952 men  and 303  participants with hearing loss. After adjusting for potential confounders in the multivariate linear regression model, the relationship between MTL and hearing thresholds was not statistically significant. Smooth curve fittings indicated a non-linear relationship between MTL and high-frequency PTA hearing threshold shifts. MTL was inversely related to high-frequency PTA to the turning point (T/S ratio = 0.82) (adjusted β−21.45, 95% CI −37.28, −5.62; Our findings revealed that MTL was associated with high-frequency PTA hearing threshold shifts of adults in the United States in a non-linear manner. Hearing loss, which is associated with lifelong adverse health consequences and affects social and economic development, is the most common sensory disability in humans . It can Telomeres are repetitive DNA sequences (TTAGGG in vertebrates) and associated proteins at the ends of chromosomes for chromosomal stability and cellular integrity . They arTo date, the results of studies on the relationship between telomere length and hearing level are quite limited and inconsistent . One stu1. The NHANES data were approved by the National Center for Health Statistics Institutional Review Board by the revised Declaration of Helsinki. Data collection procedures and examinations were performed after informed consent was obtained from all the eligible participants.Our study acquired publicly accessible data from the NHANES websiteThe NHANES is a nationally representative survey approved by the Institutional Review Board of the National Center for Health Statistics. The survey combines a series of interviews, physical examinations, and laboratory tests to collect health-related information from the general population in the United States. The population in this study was enrolled in two cycles of NHANES , as these are the only cycles containing results of the leukocyte telomere length test. A flow chart for the selection of study participants is shown in 2.DNA from the participants was purified from whole blood and stored at −80°C using standardized procedures before the MTL assay measurement. The MTL assay was performed in the laboratory at the University of California, San Francisco, using the quantitative polymerase chain reaction-based method to measure telomere length relative to standard reference DNA (telomere-to-single copy gene [T/S] ratio), as previously described in detail . More deStandardized air conduction pure-tone audiometric measurements were conducted in a sound-isolated room by trained and certificated audiologists. Air-conduction thresholds were tested in both ears of the participants at frequencies between 500 and 8,000 Hz, each with an intensity range of −10 to 120 dB. The hearing threshold was defined as the level at which participants were able to detect 50% of the signal. The 1,000 Hz frequency was tested twice in each ear to ensure quality and reliability . Pure-toPotential covariates considered in the analyses included age, body mass index (BMI), sex, race/ethnicity, education level, diabetes, hypertension, cigarette smoking, and noise exposure. Information on age, sex, race/ethnicity, education level, diabetes, and hypertension were obtained during the in-home interviews. Information on noise exposure was obtained from a pre-exam audiometric questionnaire. BMI data were recorded during the physical examination.Diabetes was determined if the participants answered responded ‘yes’ to “other than during pregnancy, ever been told by a doctor or health professional had diabetes or sugar diabetes.” The answer of “borderline” was also considered diabetes . HyperteP-value of continuous data was calculated by the weighted linear regression model and the P-value of categorical data was calculated by the weighted chi-square test. A univariate analysis was conducted to estimate potential variables , and EmpowerStats software .The 1999/2000 and 2001/2002 cycles were combined, and audiometry subsample of 4-year Mobile Examination Center weights (WTSAU4YR) of the two cycles were used to estimate more representative measures for the general population of the United States following the NHANES analytic guidelines . Categorariables . A multiariables . Three rariables . A two pP < 0.01).The baseline characteristics of the 2,027 participants  enrolled in this study were stratified by quartiles for MTL and are shown in P < 0.01) (P < 0.01), speech-frequency , and high-frequency  PTA hearing threshold shifts. However, in model II, there was no association between MTL and low-frequency , speech-frequency , and high-frequency  PTA hearing threshold shifts. When the lowest quartiles of MTL was the referent, multivariate linear  regression analyses demonstrated the βs for low-frequency PTA , speech-frequency PTA  and high-frequency PTA  in the fully adjusted model (model II). MTL showed no statistically significant relationship with hearing threshold shifts after stratification by either age, sex, or race  were significantly associated with low-, speech, and high-frequency PTA hearing thresholds  . To furt or race –3.P = 0.4913), 0.26 , and −21.45 , respectively. The corresponding effect estimates at the right of inflection point were −2.56 , −1.88 , and0.18 , respectively. The high-frequency PTA decreased with the T/S ratio up to the turning point (0.82). When the T/S ratio exceeded0.82, MTL was not associated with the high-frequency PTA . The possible mechanisms are as follows: first, telomere length is inversely associated with aging, and high-frequency PTA increases with age; and second, telomere length is closely related to inflammation, oxidative stress, and inhibition of DNA repair, which play an important role in the development of age-related hearing loss . OxidatiOur study has several strengths. The data in this study were obtained from a large and nationally representative sample from the NHANES, which were standardized and reliable. Participants with abnormal results of the otoscopic examination and poor-quality results in tympanogram or tympanogram compliance of ≤0.3 ml were excluded to avoid analyzing data for conductive or mixed hearing loss.Despite these strengths, the limitations of this study should be considered. The results of this study were not validated because the NHANES is a cross-sectional study. The data representing noise exposure was from a pre-exam audiometric questionnaire involving noise exposure 24 h before the audiometric examination, which may not have reflected the accurate noise exposure status of participants. Some potential confounders were not calculated in the models.According to the results of the NHANES data analyses, MTL was associated with high-frequency PTA hearing threshold shifts of adults in the United States in a non-linear manner. MTL might be a potential predictive biomarker for hearing loss.The original contributions presented in the study are included in the article/The studies involving human participants were reviewed and approved by National Center for Health Statistics Institutional Review Board. The patients/participants provided their written informed consent to participate in this study.LL made formal analysis of data and wrote the original draft. ZM completed the methodology. ZJ and XT completed the conceptualization, review and editing, revising, and final approval, and are accountable for all aspects. All authors have approved the final manuscript as submitted.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. The reviewer DL declared a shared affiliation with the author ZM to the handling editor at the time of review.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.


ARSG) gene have been reported to underlie USH type IV. This distinct type of USH is characterized by late-onset RP with predominantly pericentral and macular changes, and late onset SNHL without vestibular dysfunction. In this study, we describe the USH type IV phenotype in three unrelated subjects. We identified three novel pathogenic variants, two novel likely pathogenic variants, and one previously described pathogenic variant in ARSG. Functional experiments indicated a loss of sulfatase activity of the mutant proteins. Our findings confirm that ARSG variants cause the newly defined USH type IV and support the proposed extension of the phenotypic USH classification.Usher syndrome (USH) is an autosomal recessively inherited disease characterized by sensorineural hearing loss (SNHL) and retinitis pigmentosa (RP) with or without vestibular dysfunction. It is highly heterogeneous both clinically and genetically. Recently, variants in the arylsulfatase G (The online version contains supplementary material available at 10.1007/s00439-022-02441-0. Usher syndrome (USH) is an autosomal recessively inherited disease characterized by sensorineural hearing loss (SNHL) and retinitis pigmentosa (RP) with or without vestibular dysfunction. It is the leading cause of inherited deaf-blindness with an estimated prevalence of 3–17 per 100,000 individuals  was described to be associated with USH type I but this was later refuted  has been suggested to be a modifier gene of retinal disease and a contributor to digenic USH  gene (OMIM 610008) was associated with an atypical USH phenotype characterized by late-onset RP with a distinctive retinal phenotype of ring-shaped atrophy along the arcades, late-onset progressive SNHL, and no vestibular involvement   in the arylsulfatase G   and 4-methylumbelliferyl sulfate , the University Medical Center Freiburg (Germany) and the Mater Misercordiae University Hospital . All included subjects were previously seen at the out-patient clinic of these hospitals.To obtain a complete description of the subjects' phenotypes, we retrospectively collected demographic data and general medical history, ophthalmic data, audiological data, and data on vestibular function. Demographics and medical history included age, descent, comorbidities, medication use, and medical family history. For ophthalmic phenotyping, we collected ocular history, age of onset and progression of ophthalmic symptoms, best corrected visual acuity, refractive error, slit lamp examination findings, and multimodal imaging including color fundus photography, optical coherence tomography (OCT), visual field tests, electroretinography (ERG), and fundus autofluorescence. Audiological data included age of onset, type and progression of audiological symptoms, medical history of the ear, otoscopic assessment, pure tone and speech audiometry, and speech-in-noise testing. The medical history of the ear included recurrent ear infections, previous noise exposure, the use of ototoxic medication, meningitis, severe head injuries, and ear surgeries. Finally, we collected data on vestibular function by identifying whether vestibular symptoms were present and whether vestibular function had been examined. Incomplete data were supplemented with additional diagnostics if possible.0.5–4 kHz) for each subject was determined. A two-parameter logistic function was used to fit the data, i.e. agemid describes the age at which the hearing thresholds are halfway between 0 dB and the asymptotic value (fixed at 130 dB). The parameter scale represents the slope of the function at this midpoint, which was used as an estimate for the annual threshold deterioration. The calculated age of onset was defined as when the calculated hearing threshold exceeds 25 dB, defined by the WHO as abnormal hearing, and subjects could benefit from amplification  was used to analyze and plot the thresholds for pure-tone audiometry. Air conduction thresholds were used to analyze the observed severity and degree of symmetry of hearing loss and audiogram configuration. In case of an air–bone gap, the bone conduction thresholds of all audiograms of the subject in question were used instead. In addition, age-related typical audiograms (ARTA) were derived from linear regression analysis of all available audiometric data of included and previously reported subjects as described to provide insight into the rate of progression of hearing loss  and hearing impairment  was performed in the ISO15189 accredited Genome Diagnostic Laboratory of the Radboud university medical center  according to routine diagnostic procedures , CNGA1 (OMIM 123825), EYS (OMIM 612424), PDE6A (OMIM 180071), PDE6B (OMIM 180072), and RPE65 (OMIM 180069).Subject D and F were pre-screened to exclude biallelic variants in other USH-associated genes in Trinity College Dublin (Ireland) as part of the Target 5000 study . Both patient-derived missense variants were introduced by site-directed mutagenesis as previously described in the WT ARSG . The PCR product was then inserted in a pCI-NEO vector, adapted to the Gateway® cloning system as previously described . His visual acuity was relatively spared (OD (right eye) 20/25 and OS (left eye) 20/32 Snellen). Ophthalmoscopy revealed waxy pallor of the optic disc, mild attenuation of the vessels, and a preserved fovea with perifoveal retinal pigment epithelial mottling. Atrophy was present around the vascular arcades; adjacent to the atrophy, predominantly located nasally and superior to the optic disc, intraretinal bone spicules were noted . The far periphery appeared relatively preserved. OCTs showed foveal sparing with only paracentral loss of the outer retina, corresponding to the relatively mild loss of visual acuity. On fundus autofluorescence, a ring of hyperautofluorescence was visible in the posterior pole at the transition zone. The mid-periphery showed confluent areas of hypoautofluorescence with preserved autofluorescence in the far periphery. ERG revealed lower scotopic than photopic responses; both were diminished. Goldmann perimetry showed an absolute ring scotoma with intact central vision and a relatively preserved peripheral field in accordance with a normal V-4e Isopter. At the age of 42, before his RP diagnosis, subject N was diagnosed with bilateral SNHL for which he is rehabilitated with bilateral conventional hearing aids . In addition, he experienced tinnitus. Physical examination and otoscopy showed no abnormalities. Pure tone audiometry revealed bilateral moderate to severe SNHL, with air and bone conduction PTAs (0.5–4.0 kHz) of 49 and 46 dB hearing level (dB HL) (right) and 55 and 53 dB HL (left) at age 46. At age 49, there was asymmetry in the air conduction thresholds, mainly in the high frequencies to the detriment of the right. An air–bone gap was observed primarily in the right ear, which could not be explained by otoscopy or CT. The latter revealed no congenital temporal bone abnormalities. At that time, air and bone conduction PTAs were 70 and 51 dB HL (right) and 64 and 55 dB HL (left). Based on the bone conduction PTAs, the progression in three years was 5 (right) and 3 dB HL (left). The subject did not report any vestibular problems.Subject F is a 72-year-old woman of Caucasian origin, recruited at the Eye Center of the University of Freiburg, Germany. She was diagnosed with hypothyroidism earlier in life. There was no relevant medical or family history related to hearing, vision, or vestibular function. Her parents were not known to be consanguineous. This individual experienced central vision loss from the age of 40 . Visual acuity deteriorated to hand movement vision only. Ophthalmoscopy revealed a pale optic disc, mild attenuation of the vessels, and atrophy around the arcades with intraretinal bone spicules predominantly located nasally and superior to the atrophy. The far periphery appeared intact. OCT showed complete loss of the outer retinal layers. Fundus autofluorescence showed extensive hypoautofluorescence in the periphery that extended to the inner part of the vascular arcades, leaving a small ring of relative normal autofluorescence in the posterior pole. ERG revealed absence of both cone and rod responses. As the disease progressed, concentric restriction of the peripheral visual field and a central scotoma developed. Subject F also experienced progressive, bilateral SNHL since the age of 20 for which she has been using bilateral conventional hearing aids since age 31–40 . At the age of 60 and 72, pure-tone audiometry showed moderate to severe SNHL with a flat audiogram configuration and PTAs of 73 dB HL (both ears) and 90 (right) and 85 dB HL (left). There were no additional problems, notably no reported vestibular symptoms. Bilateral bithermal vestibular caloric stimulation revealed a symmetrical response of the lateral semicircular canals.Subject D is an 87-year-old man of Caucasian origin seen at the Mater Misercordiae University Hospital in Dublin, Ireland. He had pulmonary tuberculosis when he was 19 years old. Later in life, he developed gastro-esophageal reflux disease, atrial fibrillation, and benign prostatic hyperplasia. This subject was diagnosed with exotropia of the left eye in his early youth. When he was over 60 years old, a posterior subcapsular cataract was observed bilaterally. Medical and family history was uneventful, his parents were not known to be consanguineous. At the age of 51–60, he experienced night blindness and photophobia . Over time, visual acuity deteriorated to light perception in the right eye and no-light perception in the left eye at age 86. Retinal imaging revealed excavation of the nerve heads, mild attenuation of the vessels, and central atrophy connecting to atrophy around the vascular arcades. This was surrounded by a ring of intraretinal bone-spicule hyperpigmentation, nasally and superior to the disc. Fundus autofluorescence showed central hypoautofluorescence and large confluent areas of hypoautofluorescence adjacent and posterior to the vascular arcades. OCT revealed complete loss of outer retinal layers. At the age of 31–40, subject D developed bilateral SNHL for which he was rehabilitated by bilateral conventional hearing aids . No other audiological data were available or could be obtained. He reported no vestibular symptoms.Audiograms of the right and left ears of included and previously reported subjects showed a predominantly bilateral moderate to severe high-frequency SNHL . The ARTA displayed an average progression of hearing loss of 1.0–1.5 dB HL per year ; NM_014960.5:c.275T > C NP_055775.2:p.(Leu92Pro). Segregation analysis showed that these variants were present in a compound heterozygous state  as there were no unaffected relatives with both ARSG variants. The c.275T > C p.(Leu92Pro) variant is a missense variant that was predicted to be pathogenic by all used in-silico prediction tools ; NM_014960.5:c.1024C > T NP_055775.2:p.(Arg342Trp). The c.1326del p.(Ser443Alafs*12) variant is a previously described pathogenic stop-gain variant ) was identified in ARSG (NM_014960.5:c.588C > A NP_055775.2:p.(Tyr196*)), a non-canonical splice site variant in ADGRV1 ), a missense variant in MYO7A , PhyloP: 2.5 (threshold: 2.7), Grantham: 29 (threshold: 80), MutationTaster: 'Benign' and SIFT: 'Tolerated') and the SpliceAI predictions for the ADGRV1 and PCDH15 variants were low (ADGRV1: acceptor splice site loss at + 11nt (0.01/1); PCDH15: acceptor splice site gain at + 124nt (0.24/1), acceptor splice site loss at −54nt (0.02/1), donor splice site gain at + 3nt (0.19/1)). Also, SpliceAI predicted no pseudo-exon inclusion for the PCDH15 variant. Therefore, the ARSG variant was considered the strongest candidate in a gene associated with USH. Manual inspection of the sequencing reads (CRAM files) revealed indications for a deletion spanning exons 7 and 8 of ARSG. PCR and Sanger sequencing confirmed the deletion and breakpoints: NM_014960.5:c.705-3940_982 + 2952del NP_055775.2:p.(Ser235Argfs*29). PCR with a reverse primer designed to bind nucleotides deleted in the c.705-3940_982 + 2952del allele demonstrated that the c.588C > A p.(Tyr196*) variant and the deletion are in trans.Genome sequencing was initiated in subject D because no variants could be identified in genes associated with USH. Initially, four heterozygous variants in USH-associated genes were identified: a stop-gain variant in ARSG variants were either not detected or detected at low frequencies (< 0.01%) in gnomAD (Table The identified ies < 0.0% in gnomAD Table  and accoies < 0.0% in gnomAD Table . Three nAD Table  (Mistry AD Table .ARSG variant of subject N (c.275T > C p.(Leu92Pro)), followed by immunoblot analysis, revealed a modestly increased ARSG expression level compared to the WT construct , showed that the original splice donor site was lost, and that an alternative splice donor site at + 13nt in intron 10 was used. This resulted in an out of frame elongation of exon 10 and a premature stop codon   ARSG (subject F) previously revealed similar ARSG expression levels as found in constructs encoding WT ARSG, but with a slightly lower molecular weight, in line with a truncated protein. Also, a significantly lower sulfatase activity was observed than for WT ARSG  and c.705-3940_982 + 2952del p.(Ser235Argfs*29) identified in subject D confirmed the truncated proteins to be of lower molecular weight than the WT ARSG, within their respective expected ranges  mouse was shown to accumulate heparan sulfate in enlarged lysosomes and develop typical mucopolysaccharidosis-like features  involvement, as would be expected from the phenotype of the KO mice and ARSG-deficient dogs. Remarkably, a similar situation has been described for other genes causative for lysosomal storage diseases. While variants in genes associated with neuronal ceroid lipofuscinosis (CLN3 (OMIM 607042), CLN5 (OMIM 608102), and MFSD8/CLN7 (OMIM611124)) typically lead to severe neuronal dysfunction and lysosomal storage in neurons and the peripheral tissues, some variants present with isolated retina disease  are associated with mucopolysaccharidosis in the vast majority of patients, but isolated retina degeneration has also been described   had a medical history of hypothyroidism, which was not reported in previous CDH23  nor in the literature to the best of our knowledge. Second, there are cases with variants in known USH-associated genes and phenotypes that differ from the corresponding type of USH, such as an USH II phenotype caused by CDH23 variants or a phenotype with vestibular dysfunction caused by USH2A variants Supplementary file2 (DOCX 16 KB)Supplementary file3 (DOCX 24 KB)Supplementary file4 (DOCX 27 KB)S Fig. 1A) Fundus photo  showing intraretinal bone-spicules predominantly located nasally and superior to the optic disc. (B) Fundus autofluorescence image  showing a ring of hyperautofluorescence in the posterior pole at the transition zone and confluent areas of hypoautofluorescence in the mid-periphery with preserved autofluorescence in the far periphery. (C) Optical coherence tomography  showing foveal sparing with only paracentral loss of the outer retina, corresponding to the relatively mild loss of visual acuity (OD 0.8 and OS 0.6 Snellen). (D) Goldmann perimetry (at age 49 years) showing an absolute ring scotoma with intact central vision and a relatively preserved peripheral field. OD, right eye; OS left eye. Supplementary file5 (EPS 8991 KB)Retinal imaging of patient N. ; subject MOL0120 III:2, MOL0737 II, and TB55 II (Khateb 2018). dB HL, decibel hearing level. Supplementary file6 (EPS 3432 KB)S Fig. 3 SPP2 and MCM2 variants were also found in unaffected relatives. The ARSG variants were shown to be present in a compound heterozygous state. *Subject II:1 was not tested. Supplementary file7 (EPS 770 KB)Segregation analysis of subject N. The initially identifiedBelow is the link to the electronic supplementary material.


Age-related hearing loss is one of the most prevalent health conditions in older adults. Although hearing aid technology has advanced dramatically, a large percentage of older adults do not use hearing aids. This untreated hearing loss may accelerate declines in cognitive and neural function and dramatically affect the quality of life. Our previous findings have shown that the use of hearing aids improves cortical and cognitive function and offsets subcortical physiological decline. The current study tested the time course of neural adaptation to hearing aids over the course of 6 months and aimed to determine whether early measures of cortical processing predict the capacity for neural plasticity. Seventeen  older adults (mean age = 75 years) with age-related hearing loss with no history of hearing aid use were fit with bilateral hearing aids and tested in six testing sessions. Neural changes were observed as early as 2 weeks following the initial fitting of hearing aids. Increases in N1 amplitudes were observed as early as 2 weeks following the hearing aid fitting, whereas changes in P2 amplitudes were not observed until 12 weeks of hearing aid use. The findings suggest that increased audibility through hearing aids may facilitate rapid increases in cortical detection, but a longer time period of exposure to amplified sound may be required to integrate features of the signal and form auditory object representations. The results also showed a relationship between neural responses in earlier sessions and the change predicted after 6 months of the use of hearing aids. This study demonstrates rapid cortical adaptation to increased auditory input. Knowledge of the time course of neural adaptation may aid audiologists in counseling their patients, especially those who are struggling to adjust to amplification. A future comparison of a control group with no use of hearing aids that undergoes the same testing sessions as the study’s group will validate these findings. Aging can lead to sensory impairments such as age-related hearing loss, which is one of the most common sensory deficits in older adults . The gloHearing aids are the most common treatment for mild-to-moderate age-related hearing loss. Although hearing aid technology has advanced dramatically over the last decade, the Global Burden of Disease estimates suggest that there is an 83% unmet need for hearing aids globally, calculated as the proportion of individuals with moderate-to-severe hearing loss who do not use a hearing aid . Our preNew hearing aid users require time to become accustomed to their hearing aids e.g., . EvidencSeveral studies have examined perceptual adaptation in older adults who were first-time hearing aids users, but they have had differing conclusions. Some studies show significant improvement in perceptual measures over time . For exaWhile these studies have suggested that adaptation may be observed post-fitting from four to eighteen weeks up to 6 months e.g., , other sIn addition to perceptual and behavioral measures, research has been conducted to study neural changes induced by newly fit hearing aids in older adults using subcortical  and cortThe CAEP has been used to examine the effects of auditory stimulation and amplification while wearing hearing aids in normal-hearing and hearing-impaired participants e.g., . More spAs mentioned earlier, a number of studies have tracked the results of using bilateral newly fit hearing aids using CAEPs for a period of 4 weeks to 6 months in older adults. Specifically, Our previous study  showed cData from thirty-one older adults  between the ages of 60–84 years were included in this study. These data were taken from a larger research study ; their audiograms are shown in All participants in the experimental group were fit with bilateral hearing aids and tested in six testing sessions as shown in p > 0.08. The control group’s data analysis showed that there was no cortical change in amplitudes of the peaks P1, N1, and P2 between sessions 1 and 6 in quiet  or in noise . In addition, there was no significant change in latencies of the peaks P1, N1, and P2 between sessions 1 and 6 in quiet  or in noise . There were no significant differences between the control and the experimental group in session 1 in any of the cortical components across conditions  . Maximum power output measurements were conducted to ensure that the hearing aids did not exceed maximum tolerance limits. On the first day, the participants received an in-service on hearing aid use and were instructed to begin wearing their hearing aids at least 8 h per day. Participants were advised that the hearing aids were set according to their audiometric thresholds, and that for the purposes of the study aims, no changes could be made to the settings. They were also told that they would adjust to the prescribed amplification if they wore their hearing aids on a daily basis. Upon request, at the end of 6 months, changes were made to features such as gain, amplification, directionality, etc. To ensure compliance, monitoring of hearing aid use (average hours/day) was done at each follow-up session through the hearing aid data logging function available through the Widex software platform (group average = 9.31 h/day ± 2 h).The hearing aid fitting procedure was previously described in All tests were conducted in an electrically-shielded sound-attenuated booth. Participants wore their hearing aids during the recording session and were seated in an upright position at a distance of two meters from an Interacoustics SP90 speaker at 0° azimuth  was used to record responses at a sampling frequency of 2,048 Hz via a 32-channel electrode cap. The offsets for all channels were below 50 μV, and earlobes served as references. Six hundred artifact-free sweeps were collected for each condition.MATLAB  was used for offline processing. Zero-phase offline bandpass filtering was performed from 1 to 30 Hz, using a 4th-order Butterworth filter. An electro-oculography reduction method  was usedChanges across six sessions: Repeated measures analyses of variance (RMANOVA) were performed using time (6 sessions) as a within-subject factor for amplitude and latency of peaks N1 (in quiet and in noise) and P2 (in quiet and in noise), followed by planned paired t-tests. Predictive measures: As stated in the introduction, we also aimed to determine if these amplitude measures can be used by the clinician to provide information regarding potential adaptation to newly fit hearing aid individuals. Therefore, regression model analysis was conducted to determine whether earlier sessions predicted improvement in the final session. Confidence intervals  = 2.055, p = 0.006, η2p = 0.128]. Post hoc pairwise comparisons between sessions after adjusting for multiple comparisons (p = 0.031), but P2 amplitude in quiet did not increase until 6 weeks after hearing aid fitting (p = 0.033). Furthermore, a significant increase in P2 amplitudes in noise was observed in the final session—24 weeks following the initial hearing aid visit (p = 0.012) (p > 0.3). Taken together, these results demonstrate evidence of neuroplasticity in N1 amplitudes earlier (2 weeks following hearing aid fitting) than P2 amplitude changes (6 weeks after hearing aid fitting). The time course of neuroplasticity during the period of hearing aid use is reflected in F = 1.156, p = 0.334], consistent with our previous finding of no change in latency between sessions 1 and 6.The RMANOVA showed a main effect of time [parisons  showed t= 0.012) , 5, but R2 = 0.655, p = 0.004) (p = 0.01).We tested whether changes in N1 amplitude that were observed in the earlier sessions predicted the increase in amplitude in the final session (week 24), thus providing a prognosis for eventual hearing aid improvement. Therefore, we examined the amplitude of N1 in quiet at the first session along with the change in amplitude in session 2 and session 3; i.e., 2, and 4 weeks after fitting, to determine whether clinicians can use these measures in these early sessions to provide the patient with expectations regarding the adaptation process. The “Enter” method of linear regression was used since it specifies the order of variables in the model, and the independent variables were entered in the following order: amplitudes at session 1, change in amplitude at session 2 and change in amplitude at session 3, with change in amplitude at session 6 as the dependent variable. To rule out strong correlations between predictor variables, collinearity diagnostics were performed showing satisfactory variance inflation factor (highest = 1.30) and tolerance (lowest = 0.76) scores. The analysis showed that the earlier sessions highly predict variance in the sixth session (= 0.004) . Of the The 85% confidence intervals were calculated for session 1 across measures to determine the criterion for significant amplitude change in an individual see . This peThe main goal of the present study was to determine the time course of neural adaptation to hearing aids and to determine whether early measures of cortical processing predict the capacity for neural change. The current study tested neuroplastic changes induced by hearing aid use over the course of 6 months using CAEPs. Neural changes were observed as early as 2 weeks following the initial fitting of hearing aids. The results showed a neural relationship between responses in earlier sessions and the change predicted after 6 months of the use of hearing aids. These results are significant, because a period of 4 weeks is usually provided for adjustment to the hearing aids, during which the patient can decide whether or not to keep the hearing aids, and knowledge of the potential for neural adaptation may be useful in the decision making process.A previous study by the authors  reportedP2 appears to reflect stimulus detection and identification, based on the spectral information provided by temporal-lobe generators, specifically located in auditory cortices of Heschl’s gyrus e.g., . N1 geneWe note that significant increases in P2 amplitudes were observed only after session 4. Therefore, it is less likely that P2 amplitudes were affected by increased stimulus exposure or repeat testing effects, at least in the early weeks of the study, as has been reported in previous auditory training studies in normal-hearing young adults , 2014. BAs mentioned in the introduction, studies have shown mixed results concerning neural adaptation at subcortical e.g.,  and cortAge-related hearing loss is considered one of the most prevalent health conditions in older adults . AlthougThis study was a relatively small study with the aim of providing pilot data for a larger study that includes more participants and a longer adaptation period. Therefore, a larger cohort would be needed to overcome inter individual variability. Due to the limited nature of the study, it was only possible to test the control group at sessions 1 and 6. Therefore, the observed changes in the hearing aid use group may be due to repeated testing effects. Future studies should include a control group that is tested for the same number of sessions, or perhaps a delayed treatment group that includes multiple baselines. Another suggestion for future research is to conduct a similar study design with first time hearing aid users but with a parallel group of experienced users, and for a longer period of auditory rehabilitation. In addition, associating the neural findings with behavioral changes in speech perception is important, and a future study would benefit from the inclusion of perceptual/self-assessment measures at all-time points. Finally, a future study should consider employing an active listening protocol to eliminate possible confounds of watching a subtitled movie on attention-related cortical components.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author/s.The studies involving human participants were reviewed and approved by the Institutional Review Board of the University of Maryland, College Park. The patients/participants provided their written informed consent to participate in this study.HK designed the study, analyzed the data, interpreted the results, and wrote the manuscript. KJ collected the data. SA designed the study, collected the data, interpreted the results, and wrote the manuscript. All authors approved the final version of the manuscript.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.