Auditory Function and Natural History of 645 Auditory Neuropathy Patients Over a 27-Year Span in China

Over the past 30 years, significant advancements have been made in auditory neuropathy (AN) research. The study aimed to explore auditory function and the natural history of AN from neonates to adulthood based on a large Chinese AN patient population.

This retrospective case series included 645 patients diagnosed with AN at our institution, the Chinese PLA General Hospital, over a 27-year period from January 1997 to December 2023. All patients had an absent or abnormal auditory brainstem response (ABR), normal or slightly altered otoacoustic emissions and/or cochlear microphonics (CM), and binaural onset.

The study enrolled patients who were from 29 provinces and 11 different ethnic groups in China. The diagnostic rate of AN has ranged from 1 case per year to 44 diagnoses per year. The study assessed the typical auditory characteristics of individuals at various ages at diagnosis. Statistically significant differences were found in the elicitation rates of ABR, distortion product otoacoustic emissions, acoustic stapedius reflex threshold, pure-tone average, 40 Hz auditory event-related potential, and progress of speech discrimination scores in AN patients from neonates to adulthood; however, the elicitation of CM ranged from 96.36 to 100% from neonates to adulthood. A relatively large proportion of AN patients had hearing loss predominantly affecting the lower frequency range. Follow-up results showed that patients with AN had stable abnormal or absent ABR, distortion product otoacoustic emissions gradually disappeared, but CM remained stable, and poor speech discrimination scores persisted. Distinct clinical profiles were observed in patients with AN carrying pathogenic or likely pathogenic mutations, including OTOF, AIFM1, ATP1A3, WFS1 , and OPA1 . OTOF and ATP1A3 mutation carriers had early onset and poor hearing thresholds, while AIFM1 had later onset and better hearing thresholds by multiple comparisons. Interventions included hearing aids with mainly bilateral interventions, and cochlear implants with predominantly unilateral intervention. Cochlear implant recipients showed lower diagnostic and onset ages and superior aided hearing thresholds compared with hearing aid users.

Advances in disease awareness, hearing screening, and diagnostic methods have enabled early detection and diagnosis of AN. Follow-up results highlighted the importance of CM in evaluating the function of outer hair cells. AN patients experienced a higher frequency of hearing loss progression while maintaining poor, unchangeable speech recognition ability. This study elucidates the multifaceted nature of AN, thereby establishing a more comprehensive understanding of the diagnosis and management of AN. Moreover, it serves as a pivotal reference for guiding counseling and evaluating the prognoses of clinical AN patients.