Skip to main content
Top
Published in: Child's Nervous System 12/2019

01-12-2019 | Original Article

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

Authors: Esther Jack, Elisabeth Haas, Terri L. Haddix

Published in: Child's Nervous System | Issue 12/2019

Login to get access

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.
Appendix
Available only for authorised users
Literature
1.
go back to reference Fuller GN, Burger PC (1992) Pia-arachnoid (leptomeninges). In: Sternberg SS (ed) Histology for pathologists, 2nd edn. Raven Press, New York, pp 164–167 Fuller GN, Burger PC (1992) Pia-arachnoid (leptomeninges). In: Sternberg SS (ed) Histology for pathologists, 2nd edn. Raven Press, New York, pp 164–167
2.
go back to reference Mack J, Squier W, Eastman JT (2009) Anatomy and development of the meninges: implications for subdural collections and CSF circulation. Pediatr Radiol 39(3):200–210CrossRef Mack J, Squier W, Eastman JT (2009) Anatomy and development of the meninges: implications for subdural collections and CSF circulation. Pediatr Radiol 39(3):200–210CrossRef
3.
go back to reference Wu Z, Tokuda Y, Zhang XW et al (2008) Age-dependent responses of glial cells and leptomeninges during systemic inflammation. Neurobiol Dis 32:543–551CrossRef Wu Z, Tokuda Y, Zhang XW et al (2008) Age-dependent responses of glial cells and leptomeninges during systemic inflammation. Neurobiol Dis 32:543–551CrossRef
4.
go back to reference 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 30:911–917CrossRef 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 30:911–917CrossRef
5.
go back to reference 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 11:677–684CrossRef 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 11:677–684CrossRef
6.
go back to reference Murphy SLZJ, Kochanek KD (2013) Deaths: final data for 2010. Natl Vital Stat Rep 61:96 Murphy SLZJ, Kochanek KD (2013) Deaths: final data for 2010. Natl Vital Stat Rep 61:96
7.
go back to reference Soto MS, Sibson NR (2018) The multifarious role of microglia in brain metastasis. Front Cell Neurosci 12:414CrossRef Soto MS, Sibson NR (2018) The multifarious role of microglia in brain metastasis. Front Cell Neurosci 12:414CrossRef
8.
go back to reference 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):21–27CrossRef 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):21–27CrossRef
9.
go back to reference Altin JG, Sloan EK (1997) The role of CD45 and CD45-associated molecules in T cell activation. Immunol Cell Biol 75(5):430–445CrossRef Altin JG, Sloan EK (1997) The role of CD45 and CD45-associated molecules in T cell activation. Immunol Cell Biol 75(5):430–445CrossRef
10.
go back to reference 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):3955–3959 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):3955–3959
11.
go back to reference Kumar GL, Rudbeck L (2009) Demasking of antigens. In: Kumar GL, Rudbeck L (eds) Immunohistochemical (IHC) staining methods, 5th ed. Dako North America, pp 51–56 Kumar GL, Rudbeck L (2009) Demasking of antigens. In: Kumar GL, Rudbeck L (eds) Immunohistochemical (IHC) staining methods, 5th ed. Dako North America, pp 51–56
12.
go back to reference Luna L (ed) (1968) AFIP Manual of histological staining methods, 3rd edn. McGraw-Hill, New York Luna L (ed) (1968) AFIP Manual of histological staining methods, 3rd edn. McGraw-Hill, New York
14.
go back to reference 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):194–197CrossRef 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):194–197CrossRef
15.
go back to reference Ferrante L, Opdal SH (2015) Sudden infant death syndrome and the genetics of inflammation. Front Immunol 6:63CrossRef Ferrante L, Opdal SH (2015) Sudden infant death syndrome and the genetics of inflammation. Front Immunol 6:63CrossRef
16.
go back to reference 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 6:44PubMedPubMedCentral 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 6:44PubMedPubMedCentral
17.
go back to reference Goldstein RD, Trachtenberg FL, Sens MA, Harty BJ, Kinney HC (2016) Overall Postneonatal mortality and rates of SIDS. Pediatrics 137(1):e20152298CrossRef Goldstein RD, Trachtenberg FL, Sens MA, Harty BJ, Kinney HC (2016) Overall Postneonatal mortality and rates of SIDS. Pediatrics 137(1):e20152298CrossRef
18.
go back to reference Louveau A, Smirnov I, Keyes TJ et al (2015) Structural and functional features of central nervous system lymphatic vessels. Nature 523:337–341CrossRef Louveau A, Smirnov I, Keyes TJ et al (2015) Structural and functional features of central nervous system lymphatic vessels. Nature 523:337–341CrossRef
19.
go back to reference 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):762–769CrossRef 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):762–769CrossRef
20.
go back to reference Malloy MH, MacDorman M (2005) Changes in the classification of sudden unexpected death in infants: United States, 1992-2001. Pediatrics 115(5):1247–1253CrossRef Malloy MH, MacDorman M (2005) Changes in the classification of sudden unexpected death in infants: United States, 1992-2001. Pediatrics 115(5):1247–1253CrossRef
Metadata
Title
Evaluation of the presence and distribution of leptomeningeal inflammation in SIDS/SUDI cases and comparison with a hospital-based cohort
Authors
Esther Jack
Elisabeth Haas
Terri L. Haddix
Publication date
01-12-2019
Publisher
Springer Berlin Heidelberg
Published in
Child's Nervous System / Issue 12/2019
Print ISSN: 0256-7040
Electronic ISSN: 1433-0350
DOI
https://doi.org/10.1007/s00381-019-04268-z

Other articles of this Issue 12/2019

Child's Nervous System 12/2019 Go to the issue