Isolated auditory neuropathy at birth in congenital cytomegalovirus infection

Abstract

Background: Congenital cytomegalovirus (cCMV) infection is the most frequent non-genetic cause of sensorineural hearing-loss (SNHL) (i.e., hearing loss due to a cochlear and/or auditory nerve damage). It is widely accepted that SNHL at birth, when associated to cCMV symptomatic infection involving the central nervous system, benefits from antiviral therapy started in the neonatal period. Conversely, there is no consensus for antiviral treatment in congenitally infected infants diagnosed with isolated SNHL (i.e., SNHL in an otherwise asymptomatic infant) at birth. Our aim was to assess the frequency and the auditory outcome of isolated SNHL at birth due to auditory neuropathy (AN) (i.e., SNHL in a patient with normal cochlear function and auditory nerve dysfunction) in infants with cCMV infection. Methods: We retrospectively reviewed the clinical history of 60 infants, born at term, with cCMV asymptomatic infection, without additional risk factors for SNHL, and exhibiting bilateral "pass" otoacustic emissions (OAE). None of them underwent antiviral therapy. Hearing thresholds were assessed by means of Auditory Brainstem Responses (ABR). AN affected children were followed up until possible normalization of the hearing thresholds or definitive diagnosis of AN. Each infant diagnosed with monolateral or bilateral AN was classified according to the worst ear threshold. Results: In our population, the first ABR was performed at a mean age of 5.00 ± 2.79 (SD) months and AN was diagnosed in 16/60 (26.67%) infants; in 4 infants the AN was defined as mild (4/4 monolateral), moderate in 11 (5/ 11 bilateral), and severe in 1 (bilateral). The mean age at first ABR was 3.69 ± 2.80 (SD) months in the 16 babies with AN and 5.48 ± 2.66 (SD) months in the 44 infants with normal hearing (p = 0.007). All AN cases spontaneously recovered a normal auditory threshold over time. The mean length of the audiological follow-up was 32.44 ± 17.58 (SD) months (range 5-60 months). Conclusion: A delayed maturation of the auditory pathways should be considered when a mild/moderate isolated AN at birth is detected in cCMV infected infants. Prospective studies conducted on larger populations, and with a longer audiological follow-up, are needed to confirm our findings.

Is auditory neuropathy an appropriate term? A systematic literature review on its aetiology and pathogenesis

“…The ANs described after infections, among the most frequent, were those from CMV 21 and parotitis 22 .…”

Congenital Cytomegalovirus and Human Immunodeficiency Virus: Effects on Hearing, Speech and Language Development, and Clinical Outcomes in Children

“…Therefore, CIs may not provide adequate benefit for cCMV-infected individuals with brain lesions as described by MRI results because CIs provide maximum benefit for individuals with normal neural pathway functionality. Additionally, Natale et al ( 30 ) discovered cases of auditory neuropathy as a result of cCMV infection. Out of 60 cCMV-infected asymptomatic children who did not undergo medical treatment, 16 children had auditory neuropathy.…”

Hearing Loss Caused by HCMV Infection through Regulating the Wnt and Notch Signaling Pathways

“…Many viruses including HCMV, Rubella virus, lymphocytic choriomeningitis virus, HIV, herpes simplex virus, measles virus, varicella zoster virus, mumps virus and West Nile virus have been documented as the causative agents for a variety of hearing loss. Among these viruses, congenital HCMV infection is recognized as the most common cause of SNHL in infants [ 8 ].…”

“…This postponed HC loss suggests that the inflammatory response might be responsible for the HC death [ 13 , 14 , 15 , 16 , 17 ], but the cell death pathways are still unclear. Hearing loss was further demonstrated to be correlated with the expression of MCMV-induced proinflammatory cytokines and chemokines, but not the viral load in the cochlea [ 8 ]. Though MCMV and HCMV are similar, there are still considerable differences between these viruses, particularly that MCMV cannot spread through the placenta like HCMV.…”

“…Infants diagnosed with symptomatic congenitally CMV infection have improved hearing after valganciclovir therapy in their neonatal period [ 72 ]. Subsequent studies further demonstrated that this antiviral treatment also helped to prevent hearing loss in newborns with an asymptomatic congenital CMV infection [ 8 , 73 , 74 ]. However, valganciclovir only decreased viral load by 1.5 log in a small number of patients and the overall clinical benefit was modest [ 72 ].…”