Altered 5-HT2A/C receptor binding in the medulla oblongata in the sudden infant death syndrome (SIDS): Part II. Age-associated alterations in serotonin receptor binding profiles within medullary nuclei supporting cardiorespiratory homeostasis.

The failure of chemoreflexes, arousal, and/or autoresuscitation to asphyxia may underlie some sudden infant death syndrome (SIDS) cases. In Part I, we showed that some SIDS infants had altered 5-hydroxytryptamine (5-HT)2A/C receptor binding in medullary nuclei supporting chemoreflexes, arousal, and autoresuscitation. Here, using the same dataset, we tested the hypotheses that the prevalence of low 5-HT1A and/or 5-HT2A/C receptor binding (defined as levels below the 95% confidence interval of controls-a new approach), and the percentages of nuclei affected are greater in SIDS versus controls, and that the distribution of low binding varied with age of death.

Sudden Unexplained Death in Childhood: Current Understanding.

Sudden, Unexplained Death in Childhood (SUDC) is a term that encompasses apparently natural deaths in children over one year of age with no discernible cause despite a thorough assessment. Definitive underlying causes vary but most cases remain largely unexplained. Research has furthered the view that SUDC is not an accident, but rather a sentinel medical event for which a thorough postmortem investigation is indicated.

Sudden Unexplained Death in Childhood: Current Understanding.

Sudden unexplained death in childhood is a term that encompasses apparently natural deaths in children aged older than 1 year with no discernible cause despite a thorough assessment. Definitive underlying causes vary but most cases remain largely unexplained. Research has furthered the view that sudden unexplained death in childhood is not an accident, but rather a sentinel medical event for which a thorough postmortem investigation is indicated.

Altered 5-HT2A/C receptor binding in the medulla oblongata in the sudden infant death syndrome (SIDS): Part I. Tissue-based evidence for serotonin receptor signaling abnormalities in cardiorespiratory- and arousal-related circuits.

The sudden infant death syndrome (SIDS), the leading cause of postneonatal infant mortality in the United States, is typically associated with a sleep period. Previously, we showed evidence of serotonergic abnormalities in the medulla (e.g.

Medullary Serotonergic Binding Deficits and Hippocampal Abnormalities in Sudden Infant Death Syndrome: One or Two Entities?

Sudden infant death syndrome (SIDS) is understood as a syndrome that presents with the common phenotype of sudden death but involves heterogenous biological causes. Many pathological findings have been consistently reported in SIDS, notably in areas of the brain known to play a role in autonomic control and arousal. Our laboratory has reported abnormalities in SIDS cases in medullary serotonin (5-HT) receptor and within the dentate gyrus of the hippocampus.

Inconsistent classification of unexplained sudden deaths in infants and children hinders surveillance, prevention and research: recommendations from The 3rd International Congress on Sudden Infant and Child Death.

This report details the proceedings and conclusions from the 3rd International Congress on Unexplained Deaths in Infants and Children, held November 26-27, 2018 at the Radcliffe Institute at Harvard University. The Congress was motivated by the increasing rejection of the diagnosis Sudden Infant Death Syndrome (SIDS) in the medical examiner community, leading to falsely depressed reported SIDS rates and undermining the validity and reliability of the diagnosis, which remains a leading cause of infant and child mortality. We describe the diagnostic shift away from SIDS and the practical issues contributing to it.

Abnormalities in substance P neurokinin-1 receptor binding in key brainstem nuclei in sudden infant death syndrome related to prematurity and sex.

Sudden infant death syndrome (SIDS) involves failure of arousal to potentially life threatening events, including hypoxia, during sleep. While neuronal dysfunction and abnormalities in neurotransmitter systems within the medulla oblongata have been implicated, the specific pathways associated with autonomic and cardiorespiratory failure are unknown. The neuropeptide substance P (SP) and its tachykinin neurokinin-1 receptor (NK1R) have been shown to play an integral role in the modulation of homeostatic function in the medulla, including regulation of respiratory rhythm generation, integration of cardiovascular control, and modulation of the baroreceptor reflex and mediation of the chemoreceptor reflex in response to hypoxia.

Hippocampal malformation associated with sudden death in early childhood: a neuropathologic study: Part 2 of the investigations of The San Diego SUDC Research Project.

Purpose: Sudden unexplained death in childhood (SUDC), while rare, accounts for an important fraction of unexpected deaths in children >1 year of age. Previously we reported an association between febrile seizures, hippocampal maldevelopment, and sudden, unexpected deaths in young children (1-6 years), termed "hippocampal maldevelopment associated with sudden death (HMASD)." Here, we characterize in greater detail the hippocampal pathology in a large cohort of cases (n = 42) of this entity, and attempt to define possible new entities responsible for sudden, unexplained death in young children without HMASD/febrile seizure phenotypes.

Sudden unexpected death in early childhood: general observations in a series of 151 cases: Part 1 of the investigations of the San Diego SUDC Research Project.

Purpose: The purpose of this study was to determine the major subcategories and clinicopathologic features of sudden unexpected death in young children in a large retrospective cohort, and to confirm the association of sudden unexplained death in children (abbreviated by us for unexplained deaths as SUDC) with hippocampal pathology and/or febrile seizures.

Methods: We undertook analysis of a retrospective cohort of 151 cases, of which 80% (121/151) were subclassified as SUDC, 11% (16/151) as explained, 7% (10/151) as undetermined, and 3% (4/151) as seizure-related.

Results: There were no significant differences between SUDC and explained cases in postnatal, gestational, or postconceptional age, frequency of preterm birth, gender, race, or organ weights.

Cardiovascular pathology in 2 young adults with sudden, unexpected death due to coronary aneurysms from Kawasaki disease in childhood.

Purpose: Coronary artery aneurysms (CAA) may remain silent after Kawasaki disease (KD) until adulthood when myocardial ischemia can lead to sudden death. We postulated that there would be young adults with sudden, unexpected death due to CAA from KD who would have a state-mandated autopsy performed by the San Diego County Medical Examiner's Office (SDCMEO).

Methods: We reviewed all autopsy cases <35years of age from 1997 to 2012 at the SDCMEO with a cardiovascular cause of death (n=154).

Sudden unexpected death in infancy: a historical perspective.

Epidemiological, developmental and pathological research over the last 40 years has done much to unravel the enigma of sudden unexpected death in infancy (SUDI) and sudden infant death syndrome (SIDS) that has afflicted the human condition for millennia. Modifications in infant care practices based on the avoidance of risk factors identified from a consistent epidemiological profile across time and multiple locations have resulted in dramatic reductions in the incidence of SUDI and SIDS in particular. The definition of SIDS (or unexplained SUDI) has been continually refined allowing enhanced multidisciplinary research, results of which can be more reliably compared between investigators.

Serotonin metabolites in the cerebrospinal fluid in sudden infant death syndrome.

Forensic biomarkers are needed in sudden infant death syndrome (SIDS) to help identify this group among other sudden unexpected deaths in infancy. Previously, we reported multiple serotonergic (5-HT) abnormalities in nuclei of the medulla oblongata that help mediate protective responses to homeostatic stressors. As a first step toward their assessment as forensic biomarkers of medullary pathology, here we test the hypothesis that 5-HT-related measures are abnormal in the cerebrospinal fluid (CSF) of SIDS infants compared with those of autopsy controls.

Potential asphyxia and brainstem abnormalities in sudden and unexpected death in infants.

Objective: Sudden and unexplained death is a leading cause of infant mortality. Certain characteristics of the sleep environment increase the risk for sleep-related sudden and unexplained infant death. These characteristics have the potential to generate asphyxial conditions.

A prospective study of sudden unexpected infant death after reported maltreatment.

Objective: To examine whether infants reported for maltreatment face a heightened risk of sudden infant death syndrome (SIDS) and other leading causes of sudden unexpected infant death (SUID).

Study Design: Linked birth and infant death records for all children born in California between 1999 and 2006 were matched to administrative child protection data. Infants were prospectively followed from birth through death or 1 year of age.

Inheritance of febrile seizures in sudden unexplained death in toddlers.

Sudden unexplained death in toddlers has been associated with febrile seizures, family history of febrile seizures, and hippocampal anomalies. We investigated the mode of inheritance for febrile seizures in these families. A three-generation pedigree was obtained from families enrolled in the San Diego Sudden Unexplained Death in Childhood Research Project, involving toddlers with sudden unexplained death, febrile seizures, and family history of febrile seizures.

Risk factor changes for sudden infant death syndrome after initiation of Back-to-Sleep campaign.

Objective: To test the hypothesis that the profile of sudden infant death syndrome (SIDS) changed after the Back-to-Sleep (BTS) campaign initiation, document prevalence and patterns of multiple risks, and determine the age profile of risk factors.

Methods: The San Diego SIDS/Sudden Unexplained Death in Childhood Research Project recorded risk factors for 568 SIDS deaths from 1991 to 2008 based upon standardized death scene investigations and autopsies. Risks were divided into intrinsic (eg, male gender) and extrinsic (eg, prone sleep).

Myocardial infarction in a newborn heterozygous for the MTHFR C677T mutation.

Neonatal myocardial infarction secondary to congenital heart disease, anomalous coronary artery anatomy, thromboembolism, coagulopathy, birth asphyxia, and unknown causes has been previously reported. We now report an infant who suffered a massive myocardial infarction during birth, requiring extensive resuscitation and aggressive management. A thrombus, the origin of which was not detected on autopsy, was found occluding the proximal left coronary artery several hours after birth.

Application of a classification system focusing on potential asphyxia for cases of sudden unexpected infant death.

Current classification schemes for sudden unexpected infant death (SUID) may not be optimal for capturing scene events that potentially predispose to asphyxia. (1) To compare causes of death in a group of SUID cases assigned by multiple reviewers using our recently published classification scheme for SUID that is based on asphyxial risk at the death scene, and (2) To compare these newly assigned causes of death to that originally assigned by the medical examiners of record who performed the autopsies. Five reviewers independently assigned causes of death for 117 cases of SUID, including 83 originally diagnosed as sudden infant death syndrome (SIDS), accessioned into the San Diego SIDS/SUDC Research Project from the San Diego County Medical Examiner's Office.

Brainstem deficiency of the 14-3-3 regulator of serotonin synthesis: a proteomics analysis in the sudden infant death syndrome.

Impaired brainstem responses to homeostatic challenges during sleep may result in the sudden infant death syndrome (SIDS). Previously we reported a deficiency of serotonin (5-HT) and its key biosynthetic enzyme, tryptophan hydroxylase (TPH2), in SIDS infants in the medullary 5-HT system that modulates homeostatic responses during sleep. Yet, the underlying basis of the TPH2 and 5-HT deficiency is unknown.

Decreased GABAA receptor binding in the medullary serotonergic system in the sudden infant death syndrome.

γ-Aminobutyric acid (GABA) neurons in the medulla oblongata help regulate homeostasis, in part through interactions with the medullary serotonergic (5-HT) system. Previously, we reported abnormalities in multiple 5-HT markers in the medullary 5-HT system of infants dying from sudden infant death syndrome (SIDS), suggesting that 5-HT dysfunction is involved in its pathogenesis. Here, we tested the hypothesis that markers of GABAA receptors are decreased in the medullary 5-HT system in SIDS cases compared with controls.

Could intra-alveolar hemosiderin deposition in adults be used as a marker for previous asphyxial episodes in cases of autoerotic death?

Intra-alveolar hemorrhage and hemosiderin have been cited as possible markers of recent and remote asphyxial events. Little study has been undertaken of the potential significance of intra-alveolar hemosiderin in adults as a potential marker of previous sublethal asphyxial episodes. Ten cases of lethal sexual asphyxia (an entity known to be associated with repetitive sublethal asphyxial episodes) and 20 randomly selected, age- and sex-matched controls had sections of lung stained for hemosiderin.