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Evaluation of the presence and distribution of leptomeningeal inflammation in SIDS/SUDI cases and comparison with a hospital-based cohort

  • Esther JackEmail author
  • Elisabeth Haas
  • Terri L. Haddix
Original Article
  • 29 Downloads

Abstract

Introduction

Prior research demonstrates that leptomeninges of infants and late-term fetuses derived from a non-traumatic, hospital-based cohort contain a surprisingly large number of inflammatory cells and stainable iron. These were present irrespective of the findings from the general autopsy, the neuropathologic examination, and the mode of delivery.

Materials and methods

We applied a similar methodology to a sudden infant death syndrome/sudden unexpected death in infancy (SIDS/SUDI) cohort. Forty-two SIDS/SUDI cases autopsied between 2006 and 2014 by the San Diego County Medical Examiner’s Office were identified. An interpretable amount of leptomeninges from at least two areas of the brain (cerebral cortex, brain stem, cerebellum) were present in each case. Immunoperoxidase (IPOX) staining with CD45 and CD68 was performed and Perl’s method was used to detect the presence of iron. The number of immunoreactive cells per IPOX stain within the leptomeninges in each slide was manually tabulated and the density subsequently quantified. The presence or absence of stainable iron was noted.

Results

This cohort represented 22 males and 20 females ranging in age from 2 to 311 days, with relatively evenly divided modes of delivery. The examined brain sections included 32 of the cerebral cortex, 18 of the brain stem, and 36 of the cerebellum. The lengths of the examined leptomeninges ranged from 2 to 40 mm. The ranges of the number of cells per millimeter, and the standard deviations of the means were wide and varied. Overall, there was no significant difference in the number of CD45 or CD68 immunoreactive cells/millimeter between the three brain sites. Comparing this cohort to a subpopulation of hospitalized infants in our prior study, there were no significant differences between the density of inflammatory cells in the sections from the cerebral cortex and brain stem. There were differences in the CD68 densities, particularly in the cerebellar sections which may be attributable to methodological differences. Iron was identified in only a single section in this cohort but was present in most of the cases in the hospital-based cohort.

Conclusion

This study further elucidates the relevance of the presence of inflammatory cells and iron in the leptomeninges. Whether in a hospital-based or more forensically relevant population, the presence of inflammatory cells in the leptomeninges (even in great abundance) is common.

Keywords

SIDS/SUDI Infant leptomeninges Forensic science 

Notes

Acknowledgments

The authors wish to thank the San Diego County Medical Examiner’s Office for their assistance with this research.

Funding information

This study was funded in part by a Lucas Grant from the American Academy of Forensic Sciences.

Compliance with ethical standards

Conflict of interest

The authors declare no conflicts of interest for this study.

Supplementary material

381_2019_4268_MOESM1_ESM.pdf (41 kb)
ESM 1 (PDF 40 kb)

References

  1. 1.
    Fuller GN, Burger PC (1992) Pia-arachnoid (leptomeninges). In: Sternberg SS (ed) Histology for pathologists, 2nd edn. Raven Press, New York, pp 164–167Google Scholar
  2. 2.
    Mack J, Squier W, Eastman JT (2009) Anatomy and development of the meninges: implications for subdural collections and CSF circulation. Pediatr Radiol 39(3):200–210CrossRefPubMedGoogle Scholar
  3. 3.
    Wu Z, Tokuda Y, Zhang XW et al (2008) Age-dependent responses of glial cells and leptomeninges during systemic inflammation. Neurobiol Dis 32:543–551CrossRefPubMedGoogle Scholar
  4. 4.
    Jack E, Fennelly NK, Haddix T (2014) The inflammatory cellular constituents of foetal and infant leptomeninges: a survey of hospital-based autopsies without trauma. Childs Nerv Syst 30:911–917CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Willinger M, James LS, Catz C (1991) Defining the sudden infant death syndrome (SIDS): deliberations of an expert panel convened by the National Institute of Child Health and Human Development. Pediatr Pathol 11:677–684CrossRefPubMedGoogle Scholar
  6. 6.
    Murphy SLZJ, Kochanek KD (2013) Deaths: final data for 2010. Natl Vital Stat Rep 61:96Google Scholar
  7. 7.
    Soto MS, Sibson NR (2018) The multifarious role of microglia in brain metastasis. Front Cell Neurosci 12:414CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Righy C, Turon R, Freitas G et al (2018) Hemoglobin metabolism by-products are associated with an inflammatory response in patients with hemorrhagic stroke (Subprodutos do metabolismo da hemoglobina se associam com resposta inflamatória em pacientes com acidente vascular cerebral hemorrágico). Rev Bras Ter Intensiva 30(1):21–27CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Altin JG, Sloan EK (1997) The role of CD45 and CD45-associated molecules in T cell activation. Immunol Cell Biol 75(5):430–445CrossRefPubMedGoogle Scholar
  10. 10.
    Tanaka Y, Matsuwaki T, Yamanouchi K, Nishihara M (2012) Exacerbated inflammatory responses related to activated microglia after traumatic brain injury in progranulin-deficient mice. Neuroscience 122(11):3955–3959Google Scholar
  11. 11.
    Kumar GL, Rudbeck L (2009) Demasking of antigens. In: Kumar GL, Rudbeck L (eds) Immunohistochemical (IHC) staining methods, 5th ed. Dako North America, pp 51–56Google Scholar
  12. 12.
    Luna L (ed) (1968) AFIP Manual of histological staining methods, 3rd edn. McGraw-Hill, New YorkGoogle Scholar
  13. 13.
    R Core Team (2013) R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna. http://www.R-project.org/. Accessed Nov 2018Google Scholar
  14. 14.
    Filiano JJ, Kinney HC (1994) A perspective on neuropathologic findings in victims of the sudden infant death syndrome: the triple-risk model. Biol Neonate 65(3-4):194–197CrossRefPubMedGoogle Scholar
  15. 15.
    Ferrante L, Opdal SH (2015) Sudden infant death syndrome and the genetics of inflammation. Front Immunol 6:63CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Blackwell C, Moscovis S, Hall S, Burns C, Scott RJ (2015) Exploring the risk factors for sudden infant deaths and their role in inflammatory responses to infection. Front Immunol 6:44PubMedPubMedCentralGoogle Scholar
  17. 17.
    Goldstein RD, Trachtenberg FL, Sens MA, Harty BJ, Kinney HC (2016) Overall Postneonatal mortality and rates of SIDS. Pediatrics 137(1):e20152298CrossRefGoogle Scholar
  18. 18.
    Louveau A, Smirnov I, Keyes TJ et al (2015) Structural and functional features of central nervous system lymphatic vessels. Nature 523:337–341CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Shapiro-Mendoza CK, Tomashek KM, Anderson RN et al (2006) Recent national trends in sudden, unexpected infant deaths: more evidence supporting a change in classification or reporting. Am J Epidemiol 163(8):762–769CrossRefPubMedGoogle Scholar
  20. 20.
    Malloy MH, MacDorman M (2005) Changes in the classification of sudden unexpected death in infants: United States, 1992-2001. Pediatrics 115(5):1247–1253CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.School of Human SciencesUniversity of Western AustraliaCrawleyAustralia
  2. 2.SIDS/SUDI ResearchSan Diego County Medical Examiner’s OfficeSan DiegoUSA
  3. 3.Forensic Analytical Crime LabHaywardUSA

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