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Acta Neuropathologica

, Volume 122, Issue 6, pp 763–774 | Cite as

Inner ear lesions in congenital cytomegalovirus infection of human fetuses

  • Natacha Teissier
  • Anne-Lise Delezoide
  • Anne-Elisabeth Mas
  • Suonavy Khung-Savatovsky
  • Bettina Bessières
  • Jeannette Nardelli
  • Christelle Vauloup-Fellous
  • Olivier Picone
  • Nadira Houhou
  • Jean-François Oury
  • Thierry Van Den Abbeele
  • Pierre Gressens
  • Homa Adle-BiassetteEmail author
Original Paper

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.

Keywords

Congenital CMV infection Sensorineural hearing loss Potassium recycling Stria vascularis 

Notes

Acknowledgments

This work was supported by grants from the Inserm and University Paris Diderot-Paris 7. We thank Evelyne Ferrary for contributing her expertise in inner ear physiology. We also thank the technicians of the Department of Pathology and Department of Developmental Biology for their help.

Supplementary material

401_2011_895_MOESM1_ESM.tif (36.5 mb)
Supplementary Figure 1. a-d: Serial sections from case 5. a: Scala media of a cochlea displaying numerous cytomegalic cells with CMV inclusion bodies in the marginal cell layer of the stria vascularis and Reissner’s membrane (arrows) (HES). b: In situ hybridization on a serial section confirming the presence of CMV RNA in these cells. c: CK7 immunostaining showing that the infected cells are epithelial cells. d: CD8 infiltration of the stria vascularis with a few lymphocytes in Reissner’s membrane. Scale bars: 100 μ in a, c; 50 μ in d. (TIFF 37366 kb)
401_2011_895_MOESM2_ESM.tif (26.8 mb)
Supplementary Figure 2. Case 3: The non-sensory epithelial cells of the crista ampullaris expressed CK7; whereas the neurosensory epithelium delimitated by the two asterisks was not labeled. Transitory cells show focal CK7 staining on the left side, but are not infected. The infected dark cells were CK7-positive. Scale bars: 100 μ (TIFF 27419 kb)
401_2011_895_MOESM3_ESM.doc (48 kb)
Supplementary Data 1 (DOC 48 kb)

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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Natacha Teissier
    • 1
    • 2
  • Anne-Lise Delezoide
    • 3
    • 4
  • Anne-Elisabeth Mas
    • 5
  • Suonavy Khung-Savatovsky
    • 3
  • Bettina Bessières
    • 6
  • Jeannette Nardelli
    • 2
  • Christelle Vauloup-Fellous
    • 7
  • Olivier Picone
    • 8
  • Nadira Houhou
    • 9
  • Jean-François Oury
    • 4
    • 10
  • Thierry Van Den Abbeele
    • 1
    • 2
    • 4
  • Pierre Gressens
    • 2
    • 4
    • 11
  • Homa Adle-Biassette
    • 2
    • 4
    • 12
    • 13
    Email author
  1. 1.Pediatric ENT DepartmentRobert Debré Hospital, APHPParisFrance
  2. 2.Inserm UMR 676, Physiopathology and Neuroprotection of the developing brainRobert Debré HospitalParisFrance
  3. 3.Department of Developmental BiologyRobert Debré Hospital, APHPParisFrance
  4. 4.Faculté de Médecine Denis DiderotUniversité Paris 7ParisFrance
  5. 5.Department of PathologyBéclère Hospital, APHPClamartFrance
  6. 6.Department of Fetal PathologyInstitut de Puériculture de ParisParisFrance
  7. 7.Department of VirologyBéclère Hospital, APHPClamartFrance
  8. 8.Department of ObstetricsBéclère HospitalClamartFrance
  9. 9.Department of VirologyBichat-Claude Bernard Hospital, APHPParisFrance
  10. 10.Department of ObstetricsRobert Debré HospitalParisFrance
  11. 11.Department of Reproductive Biology IRDB, Perinatal Brain Injury GroupCentre for the Developing Brain, Imperial CollegeLondonUnited Kingdom
  12. 12.Department of PathologyLariboisière Hospital, APHPParisFrance
  13. 13.Homa Adle-Biassette Inserm U676Hôpital Robert DebréParisFrance

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