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

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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.

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Acknowledgments

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

Funding

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

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Correspondence to Esther Jack.

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Jack, E., Haas, E. & Haddix, T.L. Evaluation of the presence and distribution of leptomeningeal inflammation in SIDS/SUDI cases and comparison with a hospital-based cohort. Childs Nerv Syst 35, 2391–2397 (2019). https://doi.org/10.1007/s00381-019-04268-z

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