title: Dentate gyrus abnormalities in sudden unexplained death in infants: morphological marker of underlying brain vulnerability.
abstract: Sudden unexplained death in infants, including the sudden infant death syndrome, is likely due to heterogeneous causes that involve different intrinsic vulnerabilities and/or environmental factors. Neuropathologic research focuses upon the role of brain regions, particularly the brainstem, that regulate or modulate autonomic and respiratory control during sleep or transitions to waking. The hippocampus is a key component of the forebrain-limbic network that modulates autonomic/respiratory control via brainstem connections, but its role in sudden infant death has received little attention. We tested the hypothesis that a well-established marker of hippocampal pathology in temporal lobe epilepsy-focal granule cell bilamination in the dentate, a variant of granule cell dispersion-is associated with sudden unexplained death in infants. In a blinded study of hippocampal morphology in 153 infants with sudden and unexpected death autopsied in the San Diego County medical examiner's office, deaths were classified as unexplained or explained based upon autopsy and scene investigation. Focal granule cell bilamination was present in 41.2% (47/114) of the unexplained group compared to 7.7% (3/39) of the explained (control) group (p < 0.001). It was associated with a cluster of other dentate developmental abnormalities that reflect defective neuronal proliferation, migration, and/or survival. Dentate lesions in a large subset of infants with sudden unexplained death may represent a developmental vulnerability that leads to autonomic/respiratory instability or autonomic seizures, and sleep-related death when the infants are challenged with homeostatic stressors. Importantly, these lesions can be recognized in microscopic sections prepared in current forensic practice. Future research is needed to determine the relationship between hippocampal and previously reported brainstem pathology in sudden infant death.
authors.affiliation: Department of Pathology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA, hannah.kinney@childrens.harvard.edu.
authors.forename: Hannah C
authors.initials: HC
authors.lastname: Kinney
authors.forename: Jane B
authors.initials: JB
authors.lastname: Cryan
authors.forename: Robin L
authors.initials: RL
authors.lastname: Haynes
authors.forename: David S
authors.initials: DS
authors.lastname: Paterson
authors.forename: Elisabeth A
authors.initials: EA
authors.lastname: Haas
authors.forename: Othon J
authors.initials: OJ
authors.lastname: Mena
authors.forename: Megan
authors.initials: M
authors.lastname: Minter
authors.forename: Kelley W
authors.initials: KW
authors.lastname: Journey
authors.forename: Felicia L
authors.initials: FL
authors.lastname: Trachtenberg
authors.forename: Richard D
authors.initials: RD
authors.lastname: Goldstein
authors.forename: Dawna D
authors.initials: DD
authors.lastname: Armstrong
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D018891:Dentate Gyrus / Q000002:abnormalities* / Q000098:blood supply / Q000378:metabolism; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D012189:Retrospective Studies; D013398:Sudden Infant Death / Q000473:pathology*; D013702:Temporal Lobe / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D014404:Tubulin / Q000378:metabolism; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D005904:Glial Fibrillary Acidic Protein; D014404:Tubulin; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C498585:TUBB3 protein, human