Auditory Neuropathy Spectrum Disorder

Auditory neuropathy spectrum disorder (ANSD) is a hearing disorder in which outer hair cell function is normal (present otoacoustic emissions or cochlear microphonics). Neural transmission of sound from the inner hair cells, auditory nerve or brainstem is abnormal or absent (absent or severely abnormal auditory brainstem response).

It makes up about 7 to 10 percent of children with permanent hearing loss (incidence 1 to 3 per 10,000 live births, and up to 10 percent of neonatal intensive care unit graduates).

The lesion may be:

• presynaptic: inner hair cell loss, OTOF mutations encoding otoferlin (which cause temperature sensitive and stable forms), SLC17A8, and others
• synaptic: loss of ribbon synapses
• postsynaptic: auditory nerve dysplasia or deficiency, cochlear nerve hypoplasia, demyelinating neuropathy, and mutations of OPA1, DIAPH3 and others

Risk factors:

• prematurity
• hyperbilirubinaemia (exchange transfusion)
• hypoxia
• low birth weight
• ototoxic drugs (aminoglycosides)
• mechanical ventilation
• congenital cytomegalovirus infection
• genetic factors (about 40 percent with an identified genetic cause)
• family history
• neurodegenerative disorders (Charcot-Marie-Tooth disease, Friedreich ataxia, mitochondrial disease)
• cochlear nerve deficiency

The key functional deficit is impaired temporal processing. Thresholds on behavioural audiometry vary from normal to profound, but speech perception, especially in noise, is far worse than the audiogram predicts.

• Infants who pass newborn otoacoustic emission screening but have an absent or abnormal auditory brainstem response; delayed speech and language development, inconsistent responses to sound.
• Children: fluctuating responses to sound, hearing "but not understanding", poor speech recognition especially in noise, delayed or abnormal speech, and variability from day to day; in febrile illness a temperature sensitive worsening (OTOF).
• Adolescents and adults: difficulty understanding speech in noise out of proportion to pure tone thresholds, with normal-to-moderate loss on the audiogram, tinnitus rarely.
• Associated: peripheral neuropathy, balance difficulties, visual impairment (optic atrophy), cognitive and developmental delay, cerebral palsy, and other syndromic features.
• Often progressive or fluctuating.

• Auditory brainstem response (click and tone burst): absent or markedly abnormal waves with preserved cochlear microphonic (identified by reversing stimulus polarity: the response inverts, without latency change); abnormal waves with normal or only mild elevation of thresholds on behavioural testing.
• Otoacoustic emissions: present (normal outer hair cell function), though may disappear over time; contralateral suppression absent.
• Tympanometry: normal, with absent acoustic reflexes.
• Behavioural audiometry (visual reinforcement audiometry in infants, play audiometry in children, pure tone audiometry in adults), speech perception testing in quiet and in noise with word recognition scores disproportionately poor.
• Electrocochleography: summating potential enlarged with cochlear microphonic, with a prolonged negative potential (the compound action potential may be absent or abnormal), to localise the lesion.
• MRI of the internal auditory canals and brain, with thin section T2-weighted sequences in the sagittal oblique plane to assess cochlear nerve size (hypoplasia or aplasia), and CT of the temporal bone for cochlear anatomy.
• Genetic testing (OTOF, GJB2 to exclude, and a hearing loss gene panel or exome), cytomegalovirus testing, neurological and ophthalmological evaluation, and neuropathy screening (nerve conduction studies).
• Repeated testing as the pattern can change.

Management is multidisciplinary (audiology, otolaryngology, speech and language therapy, genetics, neurology, education), with early intervention to support language development.

• Early identification and intervention within 6 months of age; careful and repeated audiological follow up as responses can fluctuate.
• Communication approaches: visual communication (sign language, cued speech, lip reading) together with auditory oral training from the start, since reliance on hearing alone is unreliable; speech and language therapy; and educational support (frequency modulation system, sign language interpretation, and classroom accommodations).
• Hearing aids: a trial for children with measurable thresholds, with careful fitting and monitoring (benefit is variable, about 50 percent show some improvement), avoiding over amplification; the aid is continued only if language benefit is evident; an FM (digital remote microphone) system improves speech perception in noise.
• Cochlear implantation: indicated for children and adults with poor speech perception despite appropriately fitted hearing aids.
  • Outcomes are good in presynaptic and synaptic types (OTOF mutations: results similar to those with sensorineural deafness).
  • Outcomes are poor with cochlear nerve aplasia or hypoplasia. An auditory brainstem implant is considered for cochlear nerve aplasia in selected patients, with variable results.
  • The implant should be placed early (before age 2 to 3 years) when indicated. Electrically evoked compound action potentials and intraoperative testing are used.
• Gene therapy for OTOF-related ANSD: intracochlear adeno associated virus delivery of a functional OTOF gene has shown restored hearing in early clinical trials of children, and is offered under study protocols.
• Avoid ototoxic drugs and loud noise; vaccinations (pneumococcal, Haemophilus), and genetic counselling.
• Monitoring: audiological assessment every 3 to 6 months in children, with serial speech perception testing.
• Prognosis: variable; some children improve spontaneously (especially those with neonatal risk factors), while others have progressive or stable deficits; outcomes are best with early intervention.