Multi-site diagnosis and management of 260 patients with auditory neuropathy/dys-synchrony (auditory neuropathy spectrum disorder).

Test results and management data are summarized for 260 patients with diagnoses of Auditory Neuropathy Spectrum Disorder (ANSD). Hearing aids were tried in 85 of these patients, and 49 patients tried cochlear implants. Approximately 15% reported some benefit from hearing aids for language learning, while improvement in speech comprehension and language acquisition was reported in 85% of patients who were implanted. Approximately 5% (13/260) of the total population developed normal speech and language without intervention. Patients were diagnosed at our laboratory (n=66) or referred from other sites (n=194), and all showed absent/grossly abnormal auditory brainstem responses (ABR), often 'ringing' cochlear microphonics, and the presence or history of otoacoustic emissions. Etiologies and co-existing conditions included genetic (n=41), peripheral neuropathies (n=20), perinatal jaundice and/or anoxia and/or prematurity (n=74). These patients comprise 10% or more of hearing impaired patients; their language acquisition trajectories are generally unpredictable from their audiograms.

Absent or elevated middle ear muscle reflexes in the presence of normal otoacoustic emissions: a universal finding in 136 cases of auditory neuropathy/dys-synchrony.

We extracted a subpopulation of 136 patients (from our database of 257 AN/AD subjects) in whom middle ear muscle reflexes had been measured. None showed normal reflexes at all frequencies tested. Only three subjects showed any reflexes at 95 dB HL or below, but never at both 1 and 2 kHz in both ears whether ipsilaterally or contralaterally elicited. All the other reflex measures in these remaining 133 patients were either absent or observed above 100 dB HL, which is incongruous with their normal otoacoustic emissions throughout the frequency bands. Therefore, we urge colleagues to test ipsilateral middle ear muscle reflex at least at 1 kHz and 2 kHz in any perinatal hearing screening that depends solely on otoacoustic emissions. If the emissions are present and the reflexes are absent or elevated, an ABR may be required to properly intervene, because the management of AN/AD patients often differs drastically from what the behavioral audiogram or the ABR suggest.

Connexin 26 variants and auditory neuropathy/dys-synchrony among children in schools for the deaf.

Genetic and auditory studies of 731 children with severe-to-profound hearing loss in US schools for the deaf and 46 additional children receiving clinical services for hearing loss ranging from moderate to profound demonstrated that mutations in the connexin 26 (GJB2) and connexin 30 (GJB6) genes explain at least 12% of those with nonsyndromic sensorineural deafness. Otoacoustic emissions (OAEs) testing to detect functional outer hair cells indicated that 76 of the children had emissions and therefore may have (as yet unconfirmed) auditory neuropathy/dys-synchrony (AN/AD). Five of these children with OAEs were GJB2 homozygotes or compound heterozygotes with the genotypes 35delG/35delG, W77X/W77X, 35delG/360delGAG, 35delG/V95M, and V84M/M34T. In particular, unilateral AN/AD was confirmed in a child with moderate hearing loss and the 35delG/V95M genotype. Detecting OAEs in individuals with GJB2 mutations suggests that lack of functional gap junctions as a result of GJB2 mutations does not necessarily destroy all outer hair cell function.

Development of low-frequency tone burst versus the click auditory brainstem response.

Often ABR threshold testing employs clicks to assess high-frequency hearing, and low-frequency tone bursts to assess low-frequency sensitivity. While a maturation effect has been shown for click stimuli, similar data are lacking for low-frequency toneburst stimuli. Thus, 305 infants ranging in conceptional age (CA) from 33 weeks to 74 weeks were tested. Absolute latencies were measured for wave V at 55, 35, and 25 dB nHL in response to a click and for wave V500 in response to a 500 Hz tone burst. Major wave latency in response to 500 Hz tone bursts decreases with age and do not stabilize by 70 weeks CA. Likewise, waves III and V latencies in response to clicks decrease with age, as has been reported by others, and do not stabilize by 70 weeks CA. Wave I latency produced by clicks did not decrease with age, being mature by 33 weeks CA.

Auditory neuropathy/dys-synchrony: diagnosis and management.

Auditory brainstem responses (ABRs) and otoacoustic emissions (OAEs) are objective measures of auditory function, but are not hearing tests. Normal OAEs reflect normal cochlear outer hair cell function, and an ABR indicates a synchronous neural response. It is quite possible for a patient to have normal OAEs but absent or grossly abnormal ABR and a behavioral audiogram that is inconsistent with either test. These patients, who may constitute as much as 10% of the diagnosed deaf population, have auditory neuropathy/dys-synchrony (AN/AD). To diagnose AN/AD accurately, ABRs are obtained in response to condensation and rarefaction clicks to distinguish cochlear microphonics (CM) from neural responses. Appropriate management is confounded by variation among patients and changes in auditory function in some patients over time. Recommendations for management include visual language exposure through methods such as American Sign Language (ASL), Cued Speech, or baby signs, and closely following patients.

Patients with auditory neuropathy/dys-synchrony lack efferent suppression of transient evoked otoacoustic emissions.

Function of the olivocochlear reflex, measured by suppression of transient evoked otoacoustic emissions, is assessed in nine patients with bilateral auditory neuropathy/dys-synchrony and compared to matched control subjects with normal auditory function. TEOAEs were acquired using 65 dB peak sound pressure linear clicks with and without the presence of broad-band noise presented binaurally, ipsilaterally, or contralaterally in a forward masking paradigm. Efferent suppression differed significantly between subject groups (p < .0001). Mean suppression was less than 0.22 dB across all suppressor noise conditions for the auditory neuropathy/dys-synchrony subjects. TEOAE suppression averaged 4.47 (binaural), 2.41 (ipsilateral), and 1.52 (contralateral) dB in the control subjects. Suppression characteristics across the three suppressor conditions were also assessed in one patient with unilateral auditory neuropathy/dys-synchrony. The results suggest that poor efferent responses are related to compromised afferent input to the OCR pathway and support the use of efferent suppression of otoacoustic emissions as a differential measure of auditory function in patients with auditory neuropathy/dys-synchrony.

Olivocochlear efferent suppression in classical musicians.

Suppression of transient-evoked otoacoustic emissions was recorded from 29 members of the Louisiana Philharmonic Orchestra and 28 non-musician control subjects matched for age and gender. Binaural broad band noise was used as the suppressor stimulus in a forward masking paradigm. Results showed musicians to have significantly more suppression than non-musicians for both the right and left ears. Two possible explanations for this functional difference between groups are that moderately loud music serves as a sound conditioning stimulus and that music can be a mechanism for strengthening central auditory pathways which may influence the olivocochlear reflex arc. Possible explanations for this are discussed and ear, gender, and age differences within each group are examined. Additionally, middle-ear muscle reflex thresholds were found to be higher in musicians than non-musicians at some frequencies in some conditions.

A novel mitochondrial tRNA(Leu(UUR)) mutation in a patient with features of MERRF and Kearns-Sayre syndrome.

In a patient with clinical features of both myoclonus epilepsy ragged-red fibers (MERRF) and Kearns-Sayre syndrome (KSS), we identified a novel guanine-to-adenine mitochondrial DNA (mtDNA) mutation at nucleotide 3255 (G3255A) of the tRNA(Leu(UUR)) gene. Approximately 5% of the skeletal muscle fibers had excessive mitochondria by succinate dehydrogenase histochemistry while a smaller proportion showed cytochrome c oxidase (COX) deficiency. In skeletal muscle, activities of mitochondrial respiratory chain complexes I, I + III, II + III, and IV were reduced. The G3255A transition was heteroplasmic in all tissues tested: muscle (53%), urine sediment (67%), peripheral leukocytes (22%), and cultured skin fibroblasts (< 2%). The mutation was absent in 50 control DNA samples. Single-fiber analysis revealed a higher proportion of mutation in COX-deficient RRF (94% +/- 5, n = 25) compared to COX-positive non-RRF (18% +/- 9, n = 21). The identification of yet another tRNA(Leu(UUR)) mutation reinforces the concept that this gene is a hot-spot for pathogenic mtDNA mutations.

Auditory neuropathy/dyssynchrony: its diagnosis and management.

Patients with auditory neuropathy/dyssynchrony exhibit no auditory brain stem response (ABR), no middle ear muscle response, and both normal otoacoustic emissions or normal cochlear microphonics. An absent or grossly abnormal ABR is not always associated with deafness. In contrast, a hearing loss of 30 dB or more usually predicts absent otoacoustic emissions, but normal emissions can be seen in some patients whose behavioral audiograms imply total deafness. This article reviews the underlying physiology that makes these tests both useful and potentially misleading, and recommends steps to be considered by primary care physicians and other professionals to compensate for the vulnerabilities of each of the procedures.

The effect of midline petrous apex lesions on tests of afferent and efferent auditory function.

OBJECTIVES: Historically, audiological procedures have focused on the assessment of the afferent (ascending) cochlear-VIIIth nerve system and have, for the most part, ignored the efferent (descending) auditory system. We report afferent and efferent auditory test results for two cases with a cholesterol cyst of the right petrous apex; one lesion involves the afferent segment of the auditory system, and the second lesion involves both the afferent and efferent segments of the auditory system. These "natural experiments" provide a unique opportunity to study the effect of a space-occupying lesion of the petrous apex on afferent and efferent function of the auditory system. DESIGN: Transient evoked otoacoustic emission (TEOAE) suppression studies were performed to assess the effect of the cholesterol cyst on the efferent system of the two cases. In addition, three complementary afferent tests of brain stem auditory function were administered: 1) acoustic reflex thresholds (ARTs); 2) masking level difference (MLD); and 3) auditory brain stem response (ABR). These tests are complementary because the superior olivary complex (SOC) is involved not only in the mediation of the sound evoked efferent reflex assessed in TEOAE suppression, but in the mediation of the ARTs, the MLD, and the ABR. RESULTS: The two cases with midline petrous apex lesions, one not involving the VIII-cochlear efferent auditory system, differed from each other with regards to TEOAEs suppression, and ARTs. Specifically, the case with only afferent involvement produced normal TEOAE suppression, a normal MLD, normal ARTs, and abnormal waves III and V of the ABR, whereas the case with both afferent and efferent involvement produced abnormal TEOAE suppression, a normal MLD, abnormal ARTs, and abnormal waves III and V of the ABR. CONCLUSIONS: These cases illustrate that although several auditory tests can be mediated within the same or adjacent anatomical structures, i.e., the SOC, they may not be equally affected by the same lesion due to different physiology. Further, the TEOAE suppression paradigm is a clinically relevant test to assay the sound evoked efferent reflex that is mediated by the medial olivocochlear system of the SOC.