June 2020 rather than 8 Studies sug- 7 or simultaneous testing. 7 ANSD to occur in is estimated 4 6 in the general population is unknown. 9 The incidence of patients with auditory neuropathy or incidence The . One in 7,000 neonates evaluated through PREVALENCE. One in 7,000 cochlear synaptopathy cochlear site of lesion and functionality more available to clinical prac- site of lesion and functionality more available treatment tools have greatly improved diagnosis, tice. These a basic under- selection, and outcome prediction. Having standing this complex topic is useful for audiologists and of ENT physicians because auditory neuropathy spectrum disor- ders (ANSDs) adults, and seniors due to occur in children, note of aging, noise exposure, trauma, and disease. Take diagnosing, evaluating, in aid will that wisdom of pearls these and discussing and treatments with patients of all ages. one in 10 children with permanent hearing loss. one in 10 children gest that a considerable number of cases may occur in the well-baby population since newborn hearing screenings are typically based on otoacoustic emissions (OAEs) Figure 1. Auditory system delineating the inner hair cells (sensory), Figure and postsynaptic portions (synapse), and the spiral gan- pre- implantationglion and auditory nerve (neural). Cochlear by- a time-locked passes the sensory and synaptic portions providing signal to the neural partition. & PEARLS OF WISDOM KEY FACTS highlights relevant to practices include Research notable information on ANSD prevalence, causations, symp- toms, evaluation, testing, and treatments. newborn hearing screening has been found to have an abnor- mal auditory nerve function. auditory brainstem response (ABR)

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2 Since then, research has Since then, research 1 In some cases, auditory neu- 4 Potential disorders and sites of lesions in- Potential 3 Dr. Colucci is a clinical and forensic audiologist in private Dr. practice in Laguna Hills, CA. uditory neuropathy was first described in 1996uditory neuropathy was by MD,Arnold Starr, and colleagues as a “hearing im- and physiological test- pairment that, by behavioral with a disorder of the auditory ing, were compatible 6

The Hearing Journal The

Fortunately, advancements in auditory electrophysiology advancements in auditory electrophysiology Fortunately, Since the discovery of auditory neuropathy, researchers researchers Since the discovery of auditory neuropathy, 32 clude (1) presynaptic disorders affecting inner hair cells and clude (1) presynaptic disorders affecting inner hair cells and ribbon synapses; (2) postsynaptic disorders affecting unmy- elinated auditory nerve dendrites; (3) postsynaptic disorders affecting auditory ganglion cells and their myelinated axons af- disorders pathway neural central (4) and dendrites; and fecting the auditory brainstem. and psychophysical tests have made the identification of the and psychophysical portion of the eighth cranial nerve.” portion of the eighth

Spectrum Disorder Spectrum AuD, MA, ABA By Dennis A. Colucci, Updates on Auditory Neuropathyon Auditory Updates HEARING MATTERS HEARING found notable in hallmarks of normal outer hair cell function auditory brain- the presence of severely abnormal or absent discrimi- measurable, speech stem evoked potentials. When expected for the nation scores are proportionally lower than a patient’s hearing degree of hearing loss, complementing understand can’t but hear sound can “I (e.g., difficulty speech, especially in noise”). Also, a host of neurological, audiological, a variety of causes, and clinical features and findings reveals con- auditory and comorbidities, phenotypes, and genotypes created by auditory neuropathy desynchrony sequences. The per- of series a in resulting thereby processing, neural impairs ceptual disadvantages and compromise—and to various de- grees, disabling communication and auditory scene analysis. the ef - central site, peripheral or a occuring from a Whether temporal fects of temporal discord are universal: “Auditory processing determines our understanding our ap- of speech, a sound source, preciation of music, being able to localize and to listen to a person in a noisy crowd.” have described various sites of the lesion along the neural along the neural have described various sites of the lesion Auditory neuropathy is a condition of abnormal neu- pathway. normal of presence signals in the acoustic of encoding ral properties of the sensory transduction and amplification outer hair cells. These structures are divided into three primary partitions re- structures These synaptic, and neural sponsible for encoding sound: sensory, (Fig. 1).

ropathy may include brainstem connections such as those as those ropathy may include brainstem connections such reported in individuals with multiple brainstem neuropathies. A

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However, 10 percent of patients seen at Massachusetts Eye Mutations of the OTOF gene (otoferlin) can express as a and Ear complain of hearing difficulty in the presence of clini- transient temperature-sensitive auditory neuropathy, which cally normal hearing,10 suggesting that ANSD and central au- resolves once the increased body temperature is resolved.17,18 ditory processing disorder (CAPD) evaluations should be A gene responsible for autosomal dominant auditory neuropa- considered for this population. thy (AUNA1) was found in a family of European ancestry. The CAUSATION. Syndromic and nonsyndromic disorders average age of symptom onset was 19 years old.19 cause auditory neuropathy through synaptic and neural path- EVALUATION. Audiological testing may cover a wide va- ways. Auditory neuropathy varies by etiology, onset age, site riety of evaluations depending on the patient’s age. These of lesion, auditory behavior, and the presence or absence of may include testing of pure tones, hearing in noise, otoa- other peripheral neuropathies.11 Prematurity, low birth weight, coustic emissions with and without crossed suppres- hyperbilirubinemia, anoxia, otoferlin gene mutations, Waarden- sion, acoustic reflexes, cochlear microphonics, summating burg’s syndrome, Charcot-Marie-Tooth disease (hereditary potentials, ABR, and cortical auditory-evoked potential motor and sensory neuropathy), ototoxic drugs, infection, and (CAEP), as well as tympanometry and electrocochleography cranial nerve hypoplasia, among others, have been reported (ECochG). as risk factors. Genetic disorders account for most cases, Medical evaluation includes an MRI of the inner ears, retro- especially in children. A mild head injury can cause cranial cochlear and brainstem structures, a complete history and nerve injury, including an injury to the eighth nerve, although genetic analysis, and a physical examination. Audiometric this is less frequent.12 configurations can be downsloping, flat, or high frequency. Auditory synaptopathy impairs sound encoding at the syn- Low-frequency or reverse curve loss is more prominent, po- apses between inner hair cells and spiral ganglion neurons.3 tentially as a result of phase-locking difficulty caused by de- Should discrimination difficulty accompany normal hearing synchrony compared to higher frequencies at approximately sensitivity by standard audiometry (some with ultra-high-­ 2,000 Hz.1 frequency hearing loss) and a history of noise exposure or In some cases of auditory neuropathy, patients may have advanced aging, the patient may have cochlear synaptopathy abnormalities in the cochlear microphonic, low amplitude or hidden hearing loss.13 wave V without a wave I, and absent TEOAEs.20 Despite com- SYMPTOM. Psychophysical testing reveals auditory neu- promised ABRs, CAEPs can often be recorded in ANSD pa- ropathy results in perceptual consequences that impair tients. Emerging research highlights the application of CAEP speech discrimination and auditory scene analysis. Unlike in estimating the behavioral thresholds in this population.21 A cochlear impairments, this condition has a minor effect on slower time constant and recovery allow for better synchrony loudness, high-frequency pitch discrimination, or localization and reliability. based on level differences. On the other hand, auditory neu- Vestibular neuropathy may accompany findings of auditory ropathy patients have deficiencies in time-based perceptions and peripheral neuropathies. Some patients with abnormal such as pitch discrimination at low frequencies, temporal inte- caloric responses may be asymptomatic in the presence of gration and modulation detection, binaural beats, masking .22 The prevalence of at least one ves- paradigms, hearing signals in noise, gap detection, and lo- tibular complaint with auditory neuropathy is 20 percent.23 calization using interaural timing.14 Using the Dizziness Handicap Inventory, the severity of bal- Children with this condition may have excellent visual cog- ance complaints is reported as moderate.24 nition but exhibit poor auditory skills.15 Speech may develop The British Society of Audiology has published compre- normally or be delayed. Speech discrimination may range hensive recommendations for testing young infants who fail from no difficulty in quiet with issues hearing in noise to pro- newborn screening or considered at risk for ANSD. Testing found hearing loss in quiet.7 for this cohort starts with a 4kHz tpABR, followed by another Adults who acquire auditory neuropathy complain of diffi- test to identify sensorineural or mixed hearing loss or ANSD, culty understanding speech and deafness in background noise. such as a bone conduction ABR, 1 kHz or 0.5 kHz ABR, click They have difficulty with music perception, sound fading, and ABR, OAE, and/or cochlear microphonics, tympanometry, or localization, and often dislike noise. They may be unemployable stapedial reflexes testing.7 In premature babies, ABR retest- for certain jobs, cannot hear well on the telephone, and prefer ing over weeks and months should be conducted to identify online jobs and email for communication. those with delayed maturation. Patients with auditory neuropathy may have constant low- TREATMENT. Goals for newborns with suspected ANSD frequency bilateral tinnitus (< 1,000 Hz) with pitch matching at are to provide appropriate treatment and begin rehabilitation the greatest degree of hearing loss, typically 10 to 15 dB SL.16 within the first six months. Visual cueing is important in the In cases of comorbid peripheral neuropathy or a diagnosis early stages until the infant’s hearing level and diagnosis can of Charcot-Marie-Tooth disease (the most common inherited be established. Hearing aids, cochlear implants (CI), and re- neurological disease), hearing loss occurs several years be- habilitation options are guided by the locus of the lesion, the fore the onset of other symptoms.3 severity of synaptic degeneration, concomitant sensory loss, Auditory neuropathy may be progressive as a result of sev- neural competency, and behavioral responses. eral conditions. These include genetic mutations, mitochon- Hearing aids are not effective in many cases, although drial disorders, autoimmune anomalies, degenerative changes some studies suggest that a trial with amplification, which from aging and noise trauma, toxic metabolic disorders, and may include wireless communication, may be recommended nutritional deficits.3 based on the patient’s degree of hearing loss, age, comor-

June 2020 The Hearing Journal 33 HEARING MATTERS bidities, and behavioral factors. Amplification is typically fit to “binaural cues improve perception in noise. Screening for standard formulas. Enhanced spectral cues and low-pass residual binaural sensitivity might be important when evaluat- filtering in the prescription are suggested in some ing a patient with AN’s candidacy for hearing aids and/or cases.7 cochlear implants.”25 Regarding CIs, assessment of spiral ganglion health using Based on CAEP testing, children more likely show matura- intraoperative ECochG measurements has become one of tion effects within six months and age-appropriate­ responses the best predictors of CI outcomes. Cochlear implantation when CIs are fitted under the age of two.26 results are better when the site of lesion is sensory or synap- tic since the CI bypasses these regions to simulate the neu- References for this article can be found at http://bit.ly/HJcurrent. ral partition (Fig. 1).6 A new hypothesis suggests that

34 The Hearing Journal June 2020