Auditory Brainstem Response Assessment Research Articles

Midlife Speech Perception Deficits: Impact of Extended High-Frequency Hearing, Peripheral Neural Function, and Cognitive Abilities.

The objectives of the present study were to investigate the effects of age-related changes in extended high-frequency (EHF) hearing, peripheral neural function, working memory, and executive function on speech perception deficits in middle-aged individuals with clinically normal hearing. We administered a comprehensive assessment battery to 37 participants spanning the age range of 20 to 56 years. This battery encompassed various evaluations, including standard and EHF pure-tone audiometry, ranging from 0.25 to 16 kHz. In addition, we conducted auditory brainstem response assessments with varying stimulation rates and levels, a spatial release from masking (SRM) task, and cognitive evaluations that involved the Trail Making test (TMT) for assessing executive function and the Abbreviated Reading Span test (ARST) for measuring working memory. The results indicated a decline in hearing sensitivities at EHFs and an increase in completion times for the TMT with age. In addition, as age increased, there was a corresponding decrease in the amount of SRM. The declines in SRM were associated with age-related declines in hearing sensitivity at EHFs and TMT performance. While we observed an age-related decline in wave I responses, this decline was primarily driven by age-related reductions in EHF thresholds. In addition, the results obtained using the ARST did not show an age-related decline. Neither the auditory brainstem response results nor ARST scores were correlated with the amount of SRM. These findings suggest that speech perception deficits in middle age are primarily linked to declines in EHF hearing and executive function, rather than cochlear synaptopathy or working memory.

The human neuroprotective placental protein composition suppressing tinnitus and restoring auditory brainstem response in a rodent model of sodium salicylate-induced ototoxicity

The effect of neuroprotective placental protein composition (NPPC) on the suppression of tinnitus and the restoration of the auditory brainstem response (ABR) characteristics was explored in tinnitus-induced rats. The animals were placed into two groups: (1) the study group, rats received sodium salicylate (SS) at the dose of 200 mg/kg twice a day for two weeks, and then 0.4 mg of the NPPC per day, between the 14th and 28th days, (2) the placebo group, rats received saline for two weeks, and then the NPPC alone between the 14th and 28th days. The gap pre-pulse inhibition of the acoustic startle (GPIAS), the pre-pulse inhibition (PPI), and the ABR assessments were performed on animals in both groups three times (baseline, day 14, and 28). The GPIAS value declined after 14 consecutive days of the SS injection, while NPPC treatment augmented the GPIAS score in the study group on the 28th day. The PPI outcomes revealed no significant changes, indicating hearing preservation after the SS and NPPC administrations. Moreover, some changes in ABR characteristics were observed following SS injection, including (1) higher ABR thresholds, (2) lowered waves I and II amplitudes at the frequencies of 6, 12, and 24 kHz and wave III at the 12 kHz, (3) elevated amplitude ratios, and (4) prolongation in brainstem transmission time (BTT). All the mentioned variables returned to their normal values after applying the NPPC. The NPPC use could exert positive therapeutic effects on the tinnitus-induced rats and improve their ABR parameters.

Auditory Brainstem Responses at 6 and 8 kHz in Infants With Normal Hearing.

Normative auditory brainstem response (ABR) data for infants and young children are available for 0.25-4 kHz, limiting clinical assessment to this range. As such, the high-frequency hearing sensitivity of infants and young children remains unknown until behavioral testing can be completed, often not until late preschool or early school ages. The purpose of this study was to obtain normative ABR data at 6 and 8 kHz in young infants. Participants were 173 full-term infants seen clinically for ABR testing at 0.4-6.7 months chronological age (M = 1.4 months, SD = 1.0), 97% of whom were ≤ 12 weeks chronological age. Stimuli included 6 and 8 kHz tone bursts presented at a rate of 27.7/s or 30.7/s using Blackman window gating with six cycles (6 kHz) or eight cycles (8 kHz) rise/fall time and no plateau. Presentation levels included 20, 40, and 60 dB nHL. The ABR threshold was estimated in 5- to 10-dB steps. As previously observed with lower frequency stimuli, ABR waveforms obtained in response to 6 and 8 kHz tone bursts decreased in latency with increasing intensity and increasing age. Latency was shorter for 8-kHz tone bursts than 6-kHz tone bursts. Data tables are presented for clinical reference for infants ≤ 4 weeks, 4.1-8 weeks, and 8.1-12 weeks chronological age including median ABR latency for Waves I, III, and V and the upper and lower boundaries of the 90% prediction interval. Interpeak Latencies I-III, III-V, and I-V are also reported. The results from this study demonstrate that ABR assessment at 6 and 8 kHz is feasible for young infants within a standard clinical appointment and provide reference data for clinical interpretation of ABR waveforms for frequencies above 4 kHz.

Latency and Interpeak Interval Values of Auditory Brainstem Response in 73 Individuals with Normal Hearing.

BACKGROUND Auditory brainstem response (ABR) potential is important for audiological diagnosis, reflecting the integrity of the structures of the auditory system up to the brainstem. The click stimulus is the best known and is most used in clinical practice. However, different devices and examiners may yield distinct results, and each institution tends to use its own parameters. We aimed to analyze the latency values of wave I, III, V, and interpeak intervals I-III, III-V, I-V values obtained in assessing ABR using a new device. MATERIAL AND METHODS We performed a cross-sectional study of 73 participants with normal hearing thresholds and no hearing problems. All underwent basic audiological (air and bone conduction, Speech Recognition Threshold, Speech Recognition Index, acoustic reflex, and tympanometry) and electrophysiological evaluation (ABR assessment). RESULTS Absolute latency and interpeak values from ABR showed earlier responses in women, faster than international standards suggest. The responses were similar to other studies carried out previously, with the exception of wave I values, which were a little earlier in females. CONCLUSIONS We assessed normative data from measurement of latency values of wave I, III, V, and interpeak intervals I-III, III-V, and I-V applying 2 standard deviations in the assessment of ABR using the new Neuro-Audio/ABR device created by Neurosoft.

Noise overstimulation of young adult UMHET4 mice accelerates age-related hearing loss

Many factors contribute to hearing loss commonly found in older adults. There can be natural aging of cellular elements, hearing loss previously induced by environmental factors such as noise or ototoxic drugs as well as genetic and epigenetic influences. Even when noise overstimulation does not immediately cause permanent hearing loss it has recently been shown to increase later age-related hearing loss (ARHL). The present study further investigated this condition in the UMHET4 mouse model by comparing a small arms fire (SAF)-like impulse noise exposure that has the greatest immediate effect in more apical cochlear regions to a broadband noise (BBN) exposure that has the greatest immediate effect in more basal cochlear regions. Both noise exposures were given at levels that only induced temporary auditory brainstem response (ABR) threshold shifts (TS). Mice were noise exposed at 5 months of age followed by ABR assessment at 6, 12, 18, 21, and 24 months of age. Mice that received the SAF-like impulse noise had accelerated age-related TS at 4 kHz that appeared at 12 months of age (significantly increased compared to no-noise controls). This increased TS at 4 kHz continued at 18 and 21 months but was no longer significantly greater at 24 months of age. The SAF-like impulse noise also induced a significantly greater mean TS at 48 kHz, first appearing at 18 months of age and continuing to be significantly greater than controls at 21 and 24 months. The BBN induced a different pace and pattern of enhanced age-related ABR TS. The mean TS for the BBN group first became significantly greater than controls at 18 months of age and only at 48 kHz. It remained significantly greater than controls at 21 months but was no longer significantly greater at 24 months of age. Results, therefore, show different influences on ARHL for the two different noise exposure conditions. Noise-induced enhancement appears to provide more an acceleration than overall total increase in ARHL.

Evaluation of a Model of Long-Term Middle Ear Catheterization for Repeat Infusion Administration and Cochlear Hair Cell Injury in Guinea Pigs.

Middle ear administration has numerous applications, including antibiotherapy and gene therapy, and is increasingly used to target the auditory and vestibular systems. In animal studies, investigating repeated exposure that mimics clinical dosing regimens has remained a challenge due to the lack of suitable models. Intratympanic injections are not suitable for long-term studies due to the increased risk related to tympanic membrane rupture or scarring and repeat anesthesia events. Surgical models of middle ear catheterization previously used have not been reliable for longer than 4 weeks, resulted in elevated stress levels, and have been associated with significant changes related to the surgery and/or the presence of the catheter such as local trauma and inflammatory and degenerative processes. These complications cause decreased hearing/deafness and greatly diminish the value and accuracy of ototoxicity studies. We describe here a procedure that permits repeat dosing into the middle ear of guinea pigs and can be used to produce a model of aminoglycoside-induced hair cell injury. The innocuity of the procedures and the efficacy of the ototoxicity model were confirmed using auditory brain stem response assessment, histopathological evaluation, and cytocochleograms. Procedure-related changes were limited to minimal inflammation in the middle ear.

Early detection of neonatal hearing loss by otoacoustic emissions and auditory brainstem response over 10 years of experience

ObjectivesA number of different screening protocols for detecting neonatal hearing loss currently exist. We present our 10 years of experience with using auditory brainstem response (ABR) complementary to otoacoustic emissions (OAEs) in the three phases hearing screening process in our hospital. Furthermore, we want to demonstrate the usefulness of these screening techniques used in combination, that remain valid to identify cases of neonatal hearing loss and meet the well-established program quality criteria for these screening protocols. MethodsData were collected retrospectively from patient record forms completed on 9698 newborns from 2007 to 2017. The screening protocol for neonatal hearing loss in our centre is carried out in three phases. First phase, prior to discharge from the hospital, consists of carrying out the OAE evaluation on the newborn. Second phase is carried out in the paediatric consultation department. There, the newborns who did not pass the first phase are again studied with OAE. If this phase is not passed either, the child is referred to a third phase for the realization of ABR, in the clinical neurophysiology service. Newborns with risk factors for hearing loss, identified in the first phase, also go on to this third phase. When this hearing threshold exceeds 30 dB, it is considered abnormal. Cases with abnormal ABR, has a re-test conducted within the next six months from the initial ABR assessment. ResultsA total of 9390 (97.1%) OAEs were performed during first phase, with 8245 newborns (87.8%) passing the screening test, while 1145 children (12.1%) presented an abnormal OAE and were included in the second screening phase. Second phase involving a repeat OAE examination performed on 1077 newborns (94%). In this second phase, 941 newborns (87.3%) passed the test. Nevertheless, 136 newborns (12.6%) failing the retest and were referred to continue on to phase three. Furthermore, 181 newborns (1.8%) presented high-risk factors at birth and were also included in this third phase. However, in the registries of children referred to this phase, only 255 (80%) ABR evaluations were confirmed. In total, 227 newborns (2.3%) were missed from the first to third phases of the screening process. According to the database of the clinical neurophysiology service, ABRs evaluations were performed in 352 newborns referred between December 2007 and December 2017. Of this sample, 38.9% were boys and 61.1% were girls. From among cases underwent ABR, 34% of newborns did not pass the OAEs. The most common risk factor was prematurity (with admission to the neonatal intensive care unit for more than five days), affecting 28%. Abnormal ABRs waveforms were found in 43.9%, with 12.3% having a sensorineural hearing loss, 26.5% showing mixed hearing loss and, conductive hearing loss being present in 61.9%. Considering sensorineural hearing loss and other types of severe hearing loss, affected patients constituted only 1.7% of the total number of individuals studied. Finally, regarding quality control of the program participation in the first phase of care included 97.2% of all newborns, yielding a third phase referral rate of 2.9%, confirmation of a diagnosis before the fourth month of life in more than 90% of cases with an average of 3.4 months of age, and a hearing impairment detection rate as an outcome indicator of 4.5%. ConclusionsOur data are similar to those of previous studies on screening for hearing loss in newborns. We have demonstrated the advantages of carrying out this protocol in three phases using the otoacoustic emissions together with auditory brainstem response, diagnostic tools that remain as a Gold Standard. Also, we want to highlight and demonstrate the importance of interdisciplinary coordination between the paediatric and clinical neurophysiology services in the implementation of this screening protocol. The foregoing has allowed us to comply with the proposed quality indicators, reaching coverage percentages of more than 95%, confirming the diagnosis of hearing loss within the first six months of life and making timely referrals to benefit the newborns with hearing impairment by way of treatment and follow-up in the early stages of development, avoiding future disabilities.

The effect of bone vibrator coupling method on the neonate auditory brainstem response

Objective: The purpose of this study was to examine the effect of three bone vibrator coupling methods on the neonate auditory brainstem response (ABR).Design: A repeated measures design was employed. Three coupling techniques were utilised (i.e. hand-held, hand-held applied force gauge and elastic band). ABRs were evoked with a bone-conducted 30 dB nHL 4000 Hz CE-Chirp octave band stimulus. A temporal bone area supero-posterior auricular position for bone vibrator placement was utilised.Study Sample: Twenty-six healthy full-term neonates participated.Results: Replicated ABRs were recorded from all neonates for each coupling method. There was a statistically significant effect of coupling on wave V latency (p < 0.001) and amplitude (p < 0.001). There was no statistical difference between the elastic band and the hand-held force gauge coupling for wave V latency and amplitude (p > 0.05). However, the hand-held coupling method produced significantly longer wave V latency and smaller amplitude versus the elastic band and hand-held force gauge (p < 0.001).Conclusions: Bone vibrator coupling method affects the neonate ABR. Clinicians should be consistent with the choice of coupling while delivering controlled bone-conducted stimuli in ABR assessments in neonates and infants.

Peri-operative electrically evoked auditory brainstem response assessment of facial nerve/cochlea interaction at cochlear implantation

Objectives: Dehiscence between the cochlear otic capsule and the facial nerve canal is a rare and relatively newly described pathology. In cochlear implantation (CI), this dehiscence may lead to adverse electric facial nerve stimulation (FNS) already at low levels, rendering its use impossible. Here, we describe an assessment technique to foresee this complication.Methods: Pre- and postoperative computed tomography (CT) scans and intraoperative electrically evoked auditory brainstem response (e-ABR) measurements were analyzed in two patients with cochlear-facial dehiscence (CFD).Results: Because of the relatively low resolution, the confirmation of CFD with a clinical CT was difficult. The e-ABR displayed a large potential with 6 and 7.5 ms latency, respectively, which did not occur otherwise.Discussion: Potential strategies to resolve and manage FNS are described.Conclusion: Prediction of FNS by assessing the distance between the labyrinthine portion of the facial nerve and the cochlea is difficult using conventional CT scans. A large evoked late myogenic potential at low stimulation levels during intraoperative e-ABR measurement may foresee FNS at CI activation.

Estimation of the status of spiral ganglion neurons and Schwann cells in the auditory neural degeneration mouse using the auditory brainstem response

Conclusion: The auditory brainstem response (ABR) wave I threshold, latency and amplitude are insensitive to spiral ganglion neurons (SGNs) degeneration, but are sensitive to the degeneration of Schwann cells and can estimate the status of Schwann cells in a neural degeneration mouse model. The thorough pre-operative ABR assessment would be helpful in predicting cochlear implant performance.Objectives: This study aimed in finding a non-invasive electrophysiological method to evaluate the status of the auditory nerve and the Schwann cells in sensorineural hearing loss (SNHL) and auditory neuropathy (AN) ears, and providing useful information for candidates screening and outcome prediction in cochlear implantation.Methods: The frequency-specific acoustic ABR was recorded in mice. The immunohistochemical staining was performed to detect the SGNs and Schwann cells in mice cochlea. The correlations between ABR wave I metrics and SGNs, Schwann cells were investigated.Results: In SNHL and AN mice cochlea, statistically significant correlations between ABR wave I thresholds, latencies and amplitudes at 8, 16, and 32 kHz and their corresponding SGNs densities were found only in wave I amplitude at 8 kHz. While the ABR wave I metrics at all three frequencies showed strong significant correlations with their corresponding Schwann cells densities.

Hearing profile in Egyptian children with attention-deficit hyperactivity disorders

BackgroundAttention-deficit hyperactivity disorder (ADHD) is a common neuropsychiatric syndrome with onset in childhood, most commonly becoming more apparent during the first few years of grade school. The aim of this study is to assess peripheral hearing and central auditory processing as well as cognitive function in 30 children diagnosed with ADHD. Their age ranged from 6 to 16 years (16 males and 14 females) and their IQ of at least 70. All of them were subjected to a basic audiological evaluation, and assessment of auditory brainstem responses, slow vertex response, and P300 waves using the oddball paradigm.ResultsNo significant differences were found between pure tone thresholds and speech audiometry between the study and the control groups. There was a statistically significant increase in auditory brainstem response (ABR) absolute latencies (III and V) and interpeak latencies (I–III and I–V) at both low repetition rate and high repetition rate. Also, an increase in latencies of N1, P2, N2, and P300 latencies was observed with decreased P300 amplitude of the study group compared with the control groups. A significant mild positive correlation was found between P300 and both wave V latency and I–V interpeak latency.ConclusionThe results of this study provide more evidence of central auditory processing involvement in children with ADHD and show the role of ABR and P300 in the management of these children.

Assessment of auditory brainstem responses in hypothyroidism and hyperthyroidism

Assessment of auditory brainstem responses in hypothyroidism and hyperthyroidism

Prepulse inhibition of the acoustic startle reflex vs. auditory brainstem response for hearing assessment

The high prevalence of noise-induced and age-related hearing loss in the general population has warranted the use of animal models to study the etiology of these pathologies. Quick and accurate auditory threshold determination is a prerequisite for experimental manipulations targeting hearing loss in animal models. The standard auditory brainstem response (ABR) measurement is fairly quick and translational across species, but is limited by the need for anesthesia and a lack of perceptual assessment. The goal of this study was to develop a new method of hearing assessment utilizing prepulse inhibition (PPI) of the acoustic startle reflex, a commonly used tool that measures detection thresholds in awake animals, and can be performed on multiple animals simultaneously. We found that in control mice PPI audiometric functions are similar to both ABR and traditional operant conditioning audiograms. The hearing thresholds assessed with PPI audiometry in sound exposed mice were also similar to those detected by ABR thresholds one day after exposure. However, three months after exposure PPI threshold shifts were still evident at and near the frequency of exposure whereas ABR thresholds recovered to the pre-exposed level. In contrast, PPI audiometry and ABR wave one amplitudes detected similar losses. PPI audiometry provides a high throughput automated behavioral screening tool of hearing in awake animals. Overall, PPI audiometry and ABR assessments of the auditory system are robust techniques with distinct advantages and limitations, which when combined, can provide ample information about the functionality of the auditory system.

The impact of degree of hearing loss on auditory brainstem response predictions of behavioral thresholds.

Diagnosis of hearing loss and prescription of amplification for infants and young children require accurate estimates of ear- and frequency-specific behavioral thresholds based on auditory brainstem response (ABR) measurements. Although the overall relationship between ABR and behavioral thresholds has been demonstrated, the agreement is imperfect, and the accuracy of predictions of behavioral threshold based on ABR may depend on degree of hearing loss. Behavioral thresholds are lower than ABR thresholds, at least in part due to differences in calibration interacting with the effects of temporal integration, which are manifest in behavioral measurements but not ABR measurements and depend on behavioral threshold. Listeners with sensory hearing loss exhibit reduced or absent temporal integration, which could impact the relationship between ABR and behavioral thresholds as degree of hearing loss increases. The present study evaluated the relationship between ABR and behavioral thresholds in infants and children over a range of hearing thresholds, and tested an approach for adjusting the correction factor based on degree of hearing loss as estimated by ABR measurements. A retrospective review of clinical records was completed for 309 ears of 177 children with hearing thresholds ranging from normal to profound hearing loss and for whom both ABR and behavioral thresholds were available. Children were required to have the same middle ear status at both evaluations. The relationship between ABR and behavioral thresholds was examined. Factors that potentially could affect the relationship between ABR and behavioral thresholds were analyzed, including degree of hearing loss observed on the ABR, behavioral test method (visual reinforcement, conditioned play, or conventional audiometry), the length of time between ABR and behavioral assessments, and clinician-reported reliability of the behavioral assessment. Predictive accuracy of a correction factor based on the difference between ABR and behavioral thresholds as a function of ABR threshold was compared to the predictive accuracy achieved by two other correction approaches in current clinical use. As expected, ABR threshold was a significant predictor of behavioral threshold. The agreement between ABR and behavioral thresholds varied as a function of degree of hearing loss. The test method, length of time between assessments, and reported reliability of the behavioral test results were not related to the differences between ABR and behavioral thresholds. A correction factor based on the linear relationship between the differences in ABR and behavioral thresholds as a function of ABR threshold resulted in more accurately predicted behavioral thresholds than other correction factors in clinical use. ABR is a valid predictor of behavioral threshold in infants and children. A correction factor that accounts for the effect of degree of hearing loss on the differences between ABR and behavioral thresholds resulted in more accurate predictions of behavioral thresholds than methods that used a constant correction factor regardless of degree of hearing loss. These results are consistent with predictions based on previous research on temporal integration for listeners with hearing loss.

The role of GTF2IRD1 in the auditory pathology of Williams-Beuren Syndrome.

Williams-Beuren Syndrome (WBS) is a rare genetic condition caused by a hemizygous deletion involving up to 28 genes within chromosome 7q11.23. Among the spectrum of physical and neurological defects in WBS, it is common to find a distinctive response to sound stimuli that includes extreme adverse reactions to loud, or sudden sounds and a fascination with certain sounds that may manifest as strengths in musical ability. However, hearing tests indicate that sensorineural hearing loss (SNHL) is frequently found in WBS patients. The functional and genetic basis of this unusual auditory phenotype is currently unknown. Here, we investigated the potential involvement of GTF2IRD1, a transcription factor encoded by a gene located within the WBS deletion that has been implicated as a contributor to the WBS assorted neurocognitive profile and craniofacial abnormalities. Using Gtf2ird1 knockout mice, we have analysed the expression of the gene in the inner ear and examined hearing capacity by evaluating the auditory brainstem response (ABR) and the distortion product of otoacoustic emissions (DPOAE). Our results show that Gtf2ird1 is expressed in a number of cell types within the cochlea, and Gtf2ird1 null mice showed higher auditory thresholds (hypoacusis) in both ABR and DPOAE hearing assessments. These data indicate that the principal hearing deficit in the mice can be traced to impairments in the amplification process mediated by the outer hair cells and suggests that similar mechanisms may underpin the SNHL experienced by WBS patients.

Counting Down the ‘Tot 10’ Highlights of 2013

Counting Down the ‘Tot 10’ Highlights of 2013

Counting Down the ‘Tot 10’ Highlights of 2013

Counting Down the ‘Tot 10’ Highlights of 2013

Effect of the ketamine/xylazine anesthetic on the auditory brainstem response of adult gerbils.

The auditory brainstem response (ABR) is a test widely used to assess the integrity of the brain stem. Although it is considered to be an auditory-evoked potential that is influenced by the physical characteristics of the stimulus, such as rate, polarity and type of stimulus, it may also be influenced by the change in several parameters. The use of anesthetics may adversely influence the value of the ABR wave latency. One of the anesthetics used for ABR assessment, especially in animal research, is the ketamine/xylazine combination. Our objective was to determine the influence of the ketamine/xylazine anesthetic on the ABR latency values in adult gerbils. The ABRs of 12 adult gerbils injected with the anesthetic were collected on three consecutive days, or a total of six collections, namely: pre-collection and A, B, C, D, and E collections. Before each collection the gerbil was injected with a dose of ketamine (100 mg/kg)/xylazine (4 mg/kg). For the capture of the ABR, 2000 click stimuli were used with rarefaction polarity and 13 stimuli per second, 80 dBnHL intensity and in-ear phones. A statistically significant difference was observed in the latency of the V wave in the ABR of gerbils in the C and D collections compared to the pre-, A and E collections, and no difference was observed between the pre-, A, B, and E collections. We conclude that the use of ketamine/xylazine increases the latency of the V wave of the ABR after several doses injected into adult gerbils; thus, clinicians should consider the use of this substance in the assessment of ABR.

D-methionine ( d-met) significantly rescues noise-induced hearing loss: Timing studies

We have previously reported rescue from noise-induced auditory brainstem response (ABR) threshold shifts with d-methionine ( d-met) administration 1 h after noise exposure. The present study investigated further d-met rescue intervals at 3, 5 and 7 h post-noise exposure. Chinchillas laniger were exposed to a 6 h 105 dB sound pressure level (dB SPL) octave band noise (OBN) and then administered d-met i.p. starting 3, 5, or 7 h after noise exposure; controls received saline i.p. immediately after noise exposure. ABR assessments were performed at baseline and on post-exposure days 1 and 21. Outer hair cell (OHC) loss was measured in cochleae obtained at sacrifice 21 days post-exposure. Administration of d-met starting at any of the delay times of 3–7 h post-noise exposure significantly reduced day 21 ABR threshold shift at 2 and 4 kHz and OHC loss at all hair cell regions measured (2, 4, 6 and 8 kHz). ABR threshold shifts in the control group at 6 and 8 kHz were only 8 and 11 dB respectively allowing little opportunity to observe protection at those 2 frequencies.

Dysregulated brain creatine kinase is associated with hearing impairment in mouse models of Huntington disease

Huntington disease (HD) is a degenerative disorder caused by expanded CAG repeats in exon 1 of the huntingtin gene (HTT). Patients with late-stage HD are known to have abnormal auditory processing, but the peripheral auditory functions of HD patients have yet to be thoroughly assessed. In this study, 19 HD patients (aged 40-59 years) were assessed for hearing impairment using pure-tone audiometry and assessment of auditory brainstem responses (ABRs). PTA thresholds were markedly elevated in HD patients. Consistent with this, elevated ABR thresholds were also detected in two mouse models of HD. Hearing loss thus appears to be an authentic symptom of HD. Immunohistochemical analyses demonstrated the presence of mutant huntingtin that formed intranuclear inclusions in the organ of Corti of HD mice, which might interfere with normal auditory function. Quantitative RT-PCR and Western blot analyses further revealed reduced expression of brain creatine kinase (CKB), a major enzyme responsible for ATP regeneration via the phosphocreatine-creatine kinase (PCr-CK) system, in the cochlea of HD mice. Treatment with creatine supplements ameliorated the hearing impairment of HD mice, suggesting that the impaired PCr-CK system in the cochlea of HD mice may contribute to their hearing impairment. These data also suggest that creatine may be useful for treating the hearing abnormalities of patients with HD.