Sudden Unexplained Death in Childhood: A Neuropathology Review

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Sudden Unexplained Death in Childhood (SUDC) is the unexpected death of a child over age 12 months that remains unexplained after a thorough case investigation, including review of the child’s medical history, circumstances of death, a complete autopsy and ancillary testing (1). First defined in 2005, SUDC cases are more often male, with death occurring during a sleep period, being found prone, peak winter incidence, associated with febrile seizure history in ~28% of cases and mild pathologic changes insufficient to explain the death (1, 2). There has been little progress in understanding the causes of SUDC and no progress in prevention. Despite reductions in sudden unexpected infant death (SUID) and other causes of mortality in childhood, the rate of SUDC has increased during the past two decades (3–5). In Ireland, SUID deaths were cut in half from 1994 to 2008 while SUDC deaths more than doubled (4). Surveillance issues, including lack of standardized certification practices, affect our understanding of the true magnitude of unexplained child deaths. Mechanisms underlying SUDC, like SUID, remain largely speculative. Limited and inconsistent evidence implicates abnormalities in brainstem autonomic and serotonergic nuclei, critical for arousal, cardiorespiratory control, and reflex responses to life-threatening hypoxia or hypercarbia in sleep (6). Abnormalities in medullary serotonergic neurons and receptors, as well as cardiorespiratory brainstem nuclei occur in some SUID cases, but have never been studied in SUDC. Retrospective, small SUDC studies with non-standardized methodologies most often demonstrate minor hippocampal abnormalities, as well as focal cortical dysplasia and dysgenesis of the brainstem and cerebellum. The significance of these findings to SUDC pathogenesis remains unclear with some investigators and forensic pathologists labeling these findings as normal variants, or potential causes of SUDC. The development of preventive strategies will require a greater understanding of underlying mechanisms.

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