Blinded review of hippocampal neuropathology in sudden unexplained death in childhood reveals inconsistent observations and similarities to explained paediatric deaths.
SUDC
hippocampus
neuropathology
Journal
Neuropathology and applied neurobiology
ISSN: 1365-2990
Titre abrégé: Neuropathol Appl Neurobiol
Pays: England
ID NLM: 7609829
Informations de publication
Date de publication:
02 2022
02 2022
Historique:
received:
25
03
2021
accepted:
19
06
2021
pubmed:
25
6
2021
medline:
8
4
2022
entrez:
24
6
2021
Statut:
ppublish
Résumé
Hippocampal findings are implicated in the pathogenesis of sudden unexplained death in childhood (SUDC), although some studies have identified similar findings in sudden explained death in childhood (SEDC) cases. We blindly reviewed hippocampal histology in SUDC and SEDC controls. Hippocampal haematoxylin and eosin (H&E) slides (n = 67; 36 SUDC, 31 controls) from clinical and forensic collaborators were evaluated by nine blinded reviewers: three board-certified forensic pathologists, three neuropathologists and three dual-certified neuropathologists/forensic pathologists. Among nine reviewers, about 50% of hippocampal sections were rated as abnormal (52.5% SUDC, 53.0% controls), with no difference by cause of death (COD) (p = 0.16) or febrile seizure history (p = 0.90). There was little agreement among nine reviewers on whether a slide was within normal range (Fleiss' κ = 0.014, p = 0.47). Within reviewer groups, there were no findings more frequent in SUDC compared with controls, with variability in pyramidal neuron and dentate gyrus findings. Across reviewer groups, there was concordance for bilamination and granule cell loss. Neither SUDC (51.2%) nor control (55.9%) slides were considered contributory to determining COD (p = 0.41). The lack of an association of hippocampal findings in SUDC and controls, as well as inconsistency of observations by multiple blinded reviewers, indicates discrepancy with previous studies and an inability to reliably identify hippocampal maldevelopment associated with sudden death (HMASD). These findings underscore a need for larger studies to standardise evaluation of hippocampal findings, identifying the range of normal variation and changes unrelated to SUDC or febrile seizures. Molecular studies may help identify novel immunohistological markers that inform on COD.
Identifiants
pubmed: 34164845
doi: 10.1111/nan.12746
pmc: PMC8777468
mid: NIHMS1768028
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e12746Subventions
Organisme : NIA NIH HHS
ID : P30 AG066512
Pays : United States
Organisme : NINDS NIH HHS
ID : U01 NS090415
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG060882
Pays : United States
Informations de copyright
© 2021 British Neuropathological Society.
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