Late-Onset Auditory Neuropathy Spectrum Disorder in a 13-Year-Old: A Possible Association with Neonatal Jaundice

Abstract

This report highlights the case of a 13-year-old female diagnosed with late-onset auditory neuropathy spectrum disorder (ANSD). While newborn hearing screening programs are effective in early identification of hearing impairments, this case underscores the potential for late-onset ANSD that may be overlooked in such screenings. The case provides insights into possible pathophysiological mechanisms and emphasizes the need for continued monitoring of auditory health beyond the neonatal period. The child was born with neonatal jaundice and underwent phototherapy in the neonatal intensive care unit (NICU) for 10 days. Despite this medical history, she passed the newborn hearing screening and exhibited typical developmental milestones in auditory, speech, language, and motor domains during early childhood. At the age of 13, following a four-day episode of high fever caused by a foodborne infection, the child began experiencing difficulty hearing and understanding speech, particularly in noisy environments. Comprehensive audiological evaluation confirmed a diagnosis of auditory neuropathy spectrum disorder, suggesting a late-onset manifestation of the condition. The history of neonatal jaundice treated with phototherapy may have predisposed the child to auditory vulnerability, although the condition did not manifest during the early developmental years. The triggering role of the episode of fever suggests a potential interaction between predisposing factors and subsequent environmental or medical events. This case suggests a possible association between neonatal jaundice and late-onset ANSD, but other contributing factors cannot be ruled out. It highlights the need to address potential risk factors during counselling in newborn hearing screening programs and emphasizes the importance of periodic audiologic assessments in individuals with such risk factors.

Introduction

Auditory neuropathy spectrum disorder (ANSD), formerly known as Auditory dys-synchrony is a disorder resulting in sensorineural hearing loss which is marked by impaired eight cranial nerve functioning with a healthy cochlear outer hair cell functioning [1]. Numerous studies have investigated the potential predisposing factors for ANSD, which are broadly classified based on the time of onset: early onset and late onset [2]. Various etiologies such as perinatal infections, low APGAR, low birth weight, anoxia, hyperbilirubinemia, and genetic/syndromic conditions have been reported to be associated with early-onset ANSD [3]. Similarly, conditions such as intermittent fever, hormonal changes during and post-puberty, exposure to neurotoxic/ototoxic chemicals, genetic mutations of genes such as OTOF, GJB2 and PVJN, mitochondrial disorders, Charcot-Marie-Tooth disease have been reported to cause late-onset ANSD [3–5].

The site of lesion in ANSD can be categorized into three types: (i) pre-synaptic lesions- affecting inner hair cells and ribbon synapses, without involvement of the auditory nerve, (ii) post-synaptic lesions- involving active auditory nerve dysfunction, such as impaired synchronization of neural firing or structural damage like demyelination, or damaged axons and dendrites, and (iii) unspecified lesions- involving both pre-synaptic and post-synaptic components [6].

The pathophysiology of ANSD may include one or more of the following mechanisms: (i) functional disruption of the auditory nerve, (ii) synaptic dysfunction between inner hair cells and the auditory nerve, (iii) impaired synchronized neural firing, (iv) partial or complete demyelination, (v) dysfunction of inner hair cells, and (vi) axonal or dendritic nerve fibre loss [6].

Numerous studies highlight that newborns identified as high-risk using High Risk Registers (HRR) during newborn hearing screening are more likely to have congenital conditions such as hearing or vision deficits, cerebral palsy, intellectual disabilities, and other developmental disorders. Among these, auditory neuropathy is a notable auditory condition [6–9]. However, once an infant passes the newborn screening tests, it is often presumed that they are no longer at risk of hearing impairment. Parents and caregivers are then typically advised to monitor the child’s auditory behavioural development as well as speech and hearing milestones. This case study presents a brief report of a patient who exhibited difficulty in hearing and understanding speech in noisy environments, with symptoms emerging a few months post-puberty, with specific red flags in HRR particularly those strongly correlated with the incidence of ANSD. The article provides clinical insights into the possible mechanisms affecting the patient’s auditory system, leading to the diagnosis of late-onset ANSD.

Case Report

A 14-year-old female presented to the outpatient department of the institute with complaints of difficulty hearing in noisy environments and occasional tinnitus for the past six months. A detailed otological case history revealed that she had neonatal jaundice and was admitted to the Neonatal Intensive Care Unit (NICU) for 10 days, where she underwent phototherapy. As per the reports of the parents, the child has passed the newborn hearing screening (which primarily conducted behavioural observation audiometry and otoacoustic emission) before getting discharged from the hospital. Following her discharge, no deviations were observed in her auditory, speech, language, or motor milestones. The child was reported by her teachers to have above-average to good academic performance. At the age of 13 years and 6 months, she attained puberty. Four months later, she experienced a foodborne infection that led to a high fever (above 102 °C, as reported by her parents) and required hospitalization. Following this event, both the child and her parents reported the onset of hearing-related symptoms.

Audiological Evaluation

The audiological evaluation comprised of otoscopic evaluation, immittance audiometry (using 226 Hz probe tone), otoacoustic emission (using transient evoked otoacoustic emissions), air conduction and bone conduction hearing thresholds using pure tone audiometry (obtained for octave frequencies ranging from 250 Hz to 8 kHz for air conduction and 250 Hz to 4 kHz for bone conduction), speech audiometry (which included speech recognition thresholds and speech identification scores), speech perception in noise, tone decay test, and auditory brainstem response (ABR).

Audiological Findings

The results of each measure of audiological evaluation have been summarised in Table 1.

Table 1.

Shows the summary of findings obtained for different audiological tests

Audiological test	Finding
Otoscopy	Bilateral tympanic membrane intact
Immiitance - Tympanometry	Bilateral ‘A’ type tympanogram
Immittance - Acoustic Reflex Thresholds	Absent bilaterally
Pure tone Average (PTA)	Right- 30 dB HL, Left − 28.75-dB HL
Speech Recognition Threshold (SRT)	Right- 65 dB HL, Left − 65 dB HL
Speech Identification scores (SIS)	Right- 66%, Left − 66%
Speech Perception In Noise (SPIN)	Right- 0%, Left − 0%
Uncomfortable Levels (speech)	Right- 65%, Left − 65%
Tone Decay Test (Olsen & Noffsinger)	Right- > 100 dB HL, Left - > 100 dB HL
Transient Evoked Otoacoustic Emission (TEOAE)	Present bilaterally (refer to Fig. 1)
Auditory Brainstem Response (ABR)	Absent bilaterally (refer to Fig. 2)

Bilateral intact tympanic membrane was visualized in otoscopy, and immittance audiometry results revealed bilateral ‘A’ type tympanogram with absent acoustic reflexes. Transient acoustic emissions were present at all test frequencies with 89% reproducibility bilaterally. The TEOAE amplitude obtained for each ear has been depicted in Fig. 1. The pure tone averages (average of 500 Hz, 1 kHz, 2 kHz and 4 kHz) were 30- and 28.75-dB HL for the right and left ears respectively. The pure tone audiometric thresholds obtained for the right and left ear have been shown in Fig. 2.

Fig. 1.

shows the TEOAE amplitude obtained for right and left ears for different test frequencies

Fig. 2.

Shows the pure tone audiometric thresholds obtained for right and left ears

The speech recognition thresholds were obtained at 65 dB HL, which was in poor agreement with pure tone average values for both the ears with speech identification scores of 66% bilaterally. The speech perception in noise testing performed at 0 dB SNR revealed 0% scores bilaterally. The uncomfortable levels (UCL) for speech stimulus was > 100 dB HL, which was suggestive no significant recruitment or reduced dynamic range for hearing sensitivity. The tone decay test was performed using Olsen and Noffsinger method which revealed a positive tone decay, suggesting of faster rate of adaptation. The auditory brainstem response test findings revealed absence of peak V at 90 dB nHL for click stimulus presented at 11.1 stimuli per second. The ABR waveforms obtained for both the ears for clicks and tone burst stimuli have been depicted in Fig. 3. Bilateral mild sensorineural hearing loss (rising audiometric configuration) was the formulated provisional diagnosis based on the pure tone audiogram.

Fig. 3.

Shows the auditory brainstem response waveforms obtained for right and left ear for clicks stimulus presented at 90 dB nHL

As the child was reporting progressive nature of the hearing difficulties and considering the age of the child, periodic audiological evaluation was recommended every three months. Since the child had enough residual hearing sensitivity (as per pure tone audiogram), parents were counselled regarding the communication strategies and the possible utility of adapting assistive listening devices. Additionally, the child was referred for detailed neurological evaluation.

Discussion

A wide range of prevalence of ANSD, ranging from 0.28 to 11%, has been reported across Western countries [10]. In the Indian population [11], reported the prevalence of ANSD among individuals with sensorineural hearing impairment to be 1 out of 183. Common symptoms experienced by individuals with ANSD include difficulty understanding speech, which worsens in the presence of background noise, and challenges in sound localization. Hearing sensitivity in these individuals can vary widely, ranging from normal hearing to profound hearing loss [6, 10–11]. Lin et al., (2020) reported that 95% of cases with acquired ANSD present with symptoms at birth or during the immediate postnatal period [12]. However, this finding implies that a small percentage of individuals may develop symptoms later in life, though such cases are less common.

In the present case, peri-natal hyperbilirubinemia appears to be a possible contributing factor, potentially associated with early-life risk factors that may lead to subclinical damage without observable symptoms. Bilirubin, being neurotoxic, can accumulate in specific regions of the auditory system, such as the auditory brainstem nuclei and auditory nerve. This deposition can potentially damage critical structures, including the inner hair cells (IHC), the synaptic junctions between IHC and auditory nerve fibres, and the spiral ganglion neurons (SGN) that relay auditory signals to the brainstem [13].

Additionally, bilirubin toxicity may lead to demyelination of auditory nerve fibres, thereby disrupting the synchronized transmission of electrical signals along the auditory pathway [13]. While this mechanism is robust enough to cause early-onset damage, the extent of injury in this case may have been limited, resulting in partial or subclinical impairment. This could suggest a potential reason for the absence of noticeable symptoms during the first 13 years of life.

However, it is crucial to recognize that such subclinical damage can increase the susceptibility of the auditory nervous system to further injury, particularly following stressful events or additional risk exposures later in life.

Further factors that might have acted as triggering events for the development of auditory neuropathy include the following:

One significant possibility is the high fever that lasted for four days, after which the patient began experiencing symptoms. Temperature-dependent neuropathy has been documented in a child by [14], where auditory dysfunction was observed as a result of increased body temperature. Notably, the dysfunction resolved as the body temperature returned to normal. The underlying mechanism was attributed to temporary conduction blocks in sodium-gated channels of axons, likely secondary to axonal inflammation.

Additionally, the article suggested that neuronal dys-synchrony might arise in individuals with compromised myelination or subclinical neuronal damage. Such latent damage can become apparent when the body undergoes stressful conditions, including hormonal changes, prolonged high fever, exposure to noise, or ototoxic drugs/chemicals [14]. These stressors may exacerbate the underlying vulnerability of the auditory nervous system, leading to observable symptoms of auditory neuropathy. The aforementioned explanation can also support the second possibility for the development of acquired auditory neuropathy spectrum disorder (ANSD): hormonal changes occurring during puberty and the initial post-pubertal months. Hormonal fluctuations during these periods can act as stressors on the auditory system, particularly in individuals with pre-existing subclinical neuronal damage [3]. These factors and their corresponding pathophysiological interactions have the potential to contribute to neuronal damage on their own or may exacerbate an underlying vulnerability by disrupting the finely tuned synchronization of neural activity in the auditory pathway.

Conclusion

The study highlights the possibility of partial damage to the auditory nerve or inner ear structures resulting from peri- and post-natal events. Such damage may remain latent until triggered by specific factors later in life. This information is crucial for clinicians and otolaryngology professionals involved in newborn hearing screening programs, as it underscores the need for heightened awareness about newborns presenting with red flags in high-risk registries (HRR).

Recognizing the potential for late-onset symptoms in these cases can aid in proactive counselling for parents and caretakers. Raising awareness about this possibility equips caregivers to monitor developmental milestones more closely and seek timely interventions if symptoms arise, ultimately contributing to better long-term auditory health outcomes for the affected individuals.

Author Contributions

PP* was involved concept planning, reviewing and revising of the manuscript, analyses of the test results, RK was involved in writing the manuscript and supervision of the audiological evaluation, KS and GA were involved in carrying out the audiological tests under supervision, and writing of the manuscript.

Funding

Nil.

Code Availability

Not applicable

Declarations

Ethics Approval and Consent to Participate

All the test procedures mentioned in the case report had followed routine clinical audiological test procedures, which are adhering to the ethical guidelines of the institute. The procedures were non-invasive and non-harmful to the participant. The client and her parents were informed regarding the procedure, its need and the instructions to be followed for each test. Written consent was obtained from the parents of the child.

Consent to Participate

Written informed consent taken prior commencing the data collection.

Consent for Publication

Yes, informed content was obtained from subject for participating in the study.

Conflicts of Interest

Nil.