Inner ear lesions in congenital cytomegalovirus infection of human fetuses

Abstract

Congenital cytomegalovirus (CMV) infection is the leading cause of non-hereditary congenital sensorineural hearing loss (SNHL). The natural course and the pathophysiology of inner ear lesions during human fetal CMV infection have not yet been reported. Inner ear lesions were investigated in six CMV-infected fetuses aged 19-35 postconceptional weeks and correlated with central nervous system (CNS) lesions. All the fetuses had high viral loads in the amniotic fluid and severe visceral and CNS lesions visible by ultrasound. Diffuse lesions consisting of both cytomegalic cells containing inclusion bodies and inflammation were found within all studied structures including the inner ear, brain, other organs, and placenta, suggesting hematogenous dissemination. Cochlear infection was consistently present and predominated in the stria vascularis (5/6), whereas the supporting cells in the organ of Corti were less often involved (2/6). Vestibular infection, found in 4/6 cases, was florid; the non-sensory epithelia, including the dark cells, were extensively infected. The endolymphatic sac was infected in 1 of 3 cases. The severity of inner ear infection was correlated with the CNS lesions, confirming the neurotropism of CMV. This study documenting infection of the structures involved in endolymph secretion and potassium homeostasis in fetuses with high amniotic fluid viral loads suggests that potassium dysregulation in the endolymphatic compartment of the inner ear may lead to secondary degeneration of the sensory structures. In addition, the occurrence of SNHL depends on the intensity and duration of the viral infection and inflammation.

Vestibular Disorders in Children With Congenital Cytomegalovirus Infection

“…Autopsied pediatric CMV cases confirmed that cytomegalic cells were present in the inner ear; lesions were mainly observed in the endolymphatic compartment of the inner ear, particularly in the vestibular structures. [13][14][15][16][17][18][19][20] Little research has been carried out on vestibular disorders induced by congenital CMV, and only 2 studies are available. 21,22 Zagólski 21 suggests that the prevalence of vestibular disorders is probably underestimated and could be higher than that of hearing loss.…”

“…To date, routine inner ear investigations of these infants include classic audiometric follow-up but not vestibular testing despite strong evidence of vestibular infection. 13,16 In addition, congenital and earlyonset complete vestibular loss are known to induce severe delays in the acquisition of the first posturomotor milestones, such as the ability to hold the head stably and to sit and walk independently. 23,24 The main objective of this study was to determine the prevalence, severity, and changes over time of vestibular deficits in pediatric CMV cases and their correlation with other sensorineural disorders induced by CMV infection.…”

“…This conclusion is supported by histologic studies that show cytomegalic lesions in the cochlea as well as the vestibule. [13][14][15][16][17][18][19][20] These lesions seem particularly concentrated in the stria vascularis in the cochlea and the dark cells in the vestibule, inducing inner-ear fluid disorders that could explain progressive or delayed inner-ear dysfunction. 13 Impact on Posturomotor Development 42 or memory retention disorders.…”

“…[13][14][15][16][17][18][19][20] These lesions seem particularly concentrated in the stria vascularis in the cochlea and the dark cells in the vestibule, inducing inner-ear fluid disorders that could explain progressive or delayed inner-ear dysfunction. 13 Impact on Posturomotor Development 42 or memory retention disorders. 43 These sequelae may also be the consequence of neurologic and oculomotor disorders in CMV-infected children.…”

Immunobiology of congenital cytomegalovirus infection of the central nervous system—the murine cytomegalovirus model

“…Two recent studies on terminated fetuses have extended our knowledge about congenital HCMV infection of the inner ear. 133,134 Inflammatory cells mainly composed of activated CD8 1 T lymphocytes were more abundant in the inner ear structures, where the virus was detected within stria vascularis followed by Reissner's membrane. Inflammatory cells were also found along cochlear nerve fibers and in the spiral ganglion.…”