Auditory Neuropathy Spectrum Disorders: From Diagnosis to Treatment: Literature Review and Case Reports

Romolo Daniele De Siati, Flora Rosenzweig, Guillaume Gersdorff, Anaïs Gregoire, Philippe Rombaux, Naïma Deggouj, Romolo Daniele De Siati, Flora Rosenzweig, Guillaume Gersdorff, Anaïs Gregoire, Philippe Rombaux, Naïma Deggouj

Abstract

Auditory neuropathy spectrum disorder (ANSD) refers to a range of hearing impairments characterized by deteriorated speech perception, despite relatively preserved pure-tone detection thresholds. Affected individuals usually present with abnormal auditory brainstem responses (ABRs), but normal otoacoustic emissions (OAEs). These electrophysiological characteristics have led to the hypothesis that ANSD may be caused by various dysfunctions at the cochlear inner hair cell (IHC) and spiral ganglion neuron (SGN) levels, while the activity of outer hair cells (OHCs) is preserved, resulting in discrepancies between pure-tone and speech comprehension thresholds. The exact prevalence of ANSD remains unknown; clinical findings show a large variability among subjects with hearing impairment ranging from mild to profound hearing loss. A wide range of prenatal and postnatal etiologies have been proposed. The study of genetics and of the implicated sites of lesion correlated with clinical findings have also led to a better understanding of the molecular mechanisms underlying the various forms of ANSD, and may guide clinicians in better screening, assessment and treatment of ANSD patients. Besides OAEs and ABRs, audiological assessment includes stapedial reflex measurements, supraliminal psychoacoustic tests, electrocochleography (ECochG), auditory steady-state responses (ASSRs) and cortical auditory evoked potentials (CAEPs). Hearing aids are indicated in the treatment of ANSD with mild to moderate hearing loss, whereas cochlear implantation is the first choice of treatment in case of profound hearing loss, especially in case of IHC presynaptic disorders, or in case of poor auditory outcomes with conventional hearing aids.

Keywords: ANSD; auditory neuropathy spectrum disorder; auditory synaptopathy; cochlear implant; genetics; hidden hearing loss.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Audiological assessment in a 5-year-old child with auditory neuropathy spectrum disorder (ANSD) caused by neonatal hypoxia. Poor unaided pure-tone perception (a, gray line) was restored with hearing aids ((a), black line). Panel (b) displays auditory brainstem responses (ABRs) evoked by clicks presented in rarefaction (R) and condensation (C) polarities and the subtraction and summation of R and C (R − C and R + C, respectively), showing detectable cochlear microphonic (CM) and absence of waves V. Electrocochleography (ECochG) recorded through a transtympanic electrode on the promontory wall using 1000 Hz tone burst presented in alternated R and C polarities at a rate of 14.3 s (c) shows a large summating potential (SP). Auditory steady-state responses (ASSRs) thresholds (d) are present in the left (X) more than in the right (O) ear.
Figure 2
Figure 2
Audiological assessment in 8-year-old patient with CAPOS syndrome. CAPOS is an acronym for Cerebellar ataxia, Areflexia, Pes cavus, Optic atrophy and Sensorineural hearing loss. Unaided pure tonal thresholds in both ears are shown in (a). The tonal hearing thresholds remain poor in the right ear aided by an acoustical hearing aid ((b), gray line) but are clearly improved in the left ear by cochlear implant ((b), black line). Speech perception was poor in unaided condition ((c), 10% gray dot at 60dB), it was partially improved by acoustical hearing aids ((c), gray line) but became significantly better with cochlear implant ((c), black line). abnormal auditory brainstem responses (ABRs) (d) show the responses evoked by clicks presented in rarefaction (R) and condensation (C) phase and the subtraction of R and C (R − C), highlighting the cochlear microphonic (CM) and the lack of waves V in the summation (R + C). Auditory steady-state responses (ASSRs) thresholds (e) are present in the left (X) more than in the right (O) ear.
Figure 3
Figure 3
Distribution of pure-tone audiometry threshold (a) and (when possible) speech audiometry threshold for disyllabic words (b) in 14 patients aged between 5 and 48 years with auditory neuropathy spectrum disorder (ANSD). Etiologies of ANSD vary among patients. The figure is intended to show the large variability in hearing ability among patients with ANSD.
Figure 4
Figure 4
Audiological assessment in an adult patient with auditory neuropathy spectrum disorder (ANSD) and bilateral cochlear nerve atrophy. Unaided thresholds for pure-tone audiometry ((a), black line for right ear, gray line for left ear) and speech audiometry ((b), black line for right ear, gray line for left ear) in quiet are good. Otoacoustic emissions (OAEs) are present bilaterally in both temporal/intensity recordings (left panel in (c) for right ear, left panel in (d) for left ear) and spectral analysis (right panel in (c) for right ear, right panel in (d) for left ear); on the other hand, auditory brainstem responses (ABRs) are abnormal with no clear cochlear microphonic (CM) ((e) for right ear, (f) for left ear).
Figure 5
Figure 5
Auditory brainstem responses (ABRs) in a 26-week preterm newborn with auditory neuropathy spectrum disorder (ANSD). Three-month ABRs (a) show small early components, whereas a cochlear microphonic (CM) was detectable 9 months later (b), suggesting a late, although partial, maturation. Auditory steady-state responses (ASSRs) remain absent in both ears.
Figure 6
Figure 6
Audiological assessment in adult with acquired auditory neuropathy spectrum disorder (ANSD) caused by bilateral cochlear nerve hypotrophia of unknown etiology. Unaided pure tone ((a), black line for right ear, gray line for left ear) and speech ((b), both ears in free field) thresholds are poor, with no improvement with hearing aids. Electrocochleography (ECochG) recorded after clicks at 90 dB and at a rate of 14.3 s ((c), grand average, above; superimposed, below) shows preserved summating potential (SP) and compound action potential (CAP). ECochG responses to tone-burst stimuli at different frequencies ((d), grand averages for 8, 4, 3, 2 and 1 kHz) show a large SP. Auditory brainstem responses (ABRs) are absent, except for the cochlear microphonic (CM) (e). The 3-Tesla magnetic resonance imaging of the right ear without contrast (f) shows the hypoplasia of the cochlear nerve.
Figure 7
Figure 7
Audiological assessment in a subject with Brown–Vialetto–Van Laere syndrome-related auditory neuropathy spectrum disorder (ANSD), resulting in neural impairment of the 8th and 12th cranial nerves and the optic nerves. Unaided pure-tone audiometry ((a), both ears) shows bilateral hearing loss mainly for low frequencies. Unaided free field speech discrimination is poor ((b), 10% gray dot at 80 dB). Aided tonal and speech perception outcomes with acoustical hearing aids remain poor and comparable to unaided perception. The latter clearly improves after cochlear implantation (CI) ((b), black line). Otoacoustic emissions (OAEs) are present ((c), spectral analysis of OAEs in the white area, compared to noise in the black area), whereas auditory brainstem responses (ABRs) synchronization was abnormal with no wave V but a clear cochlear microphonic (CM) in both rarefaction (R) and condensation (C) polarities and in the subtraction R − C (d). Cortical auditory evoked responses (e) show a P3 complex after stimulation with an oddball paradigm and in selective attentive conditions only, even if no recordable N100 or P200 waves are present in responses to the frequent stimuli (not shown).
Figure 8
Figure 8
Audiological assessment in a 14-year-old child with auditory neuropathy spectrum disorder (ANSD) features occurring with severe hearing loss. Her medical history includes a 35-week preterm birth after an intrahepatic cholestasis of pregnancy, with normal birth weight but neonatal hypoxia requiring 3 weeks of stay in neonatal intensive care unit. Hearing aids were fitted in early infancy. Besides poor sounds recognition and speech perception, speech development was good in the lexical and morphosyntactic fields. Unaided tonal thresholds ((a), gray line for right ear, black line for left ear) and unaided speech discrimination (b) are poor. Aided pure-tone audiometry (c) and speech perception (d) with hearing aids are clearly improved, allowing a good development of language skills and learning abilities. Auditory brainstem responses (ABRs) elicited by clicks at 90 dB show small cochlear microphonic (CM) (e). Auditory steady-state responses (ASSRs) (f) are detected for 500 Hz at the right ear.
Figure 9
Figure 9
Audiological assessment in a 14-years-old male with auditory neuropathy spectrum disorder (ANSD). His medical history includes neonatal hyperbilirubinemia and low birth weight. Despite early hearing aids fitting, speech development was delayed. He shows residual pure-tone hearing thresholds ((a), gray line) and poor speech discrimination ((b), gray line) in the left ear. After left-ear cochlear implantation, aided tonal ((a), black line) and speech ((b), black line) thresholds show good auditory outcomes. Auditory brainstem responses (ABRs) at left ear are absent (c). However, speech perception in noise, such as during school activities, remains poor.

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