SCN1A variants associated with sudden infant death syndrome.

We identified SCN1A variants in 2 infants who died of sudden infant death syndrome (SIDS) with hippocampal abnormalities from an exome sequencing study of 10 cases of SIDS but no history of seizures. One harbored SCN1A G682V, and the other had 2 SCN1A variants in cis: L1296M and E1308D, a variant previously associated with epilepsy. Functional evaluation in a heterologous expression system demonstrated partial loss of function for both G682V and the compound variant L1296M/E1308D. Our cases represent a novel association between SCN1A and SIDS, extending the SCN1A spectrum from epilepsy to SIDS. Our findings provide insights into SIDS and support genetic evaluation focused on epilepsy genes in SIDS.

A pediatric fatality due to accidental hydromorphone ingestion.

BACKGROUND: Death due to prescription opioid exposure has increased dramatically in North America. Currently, there is a lack of literature detailing potentially lethal doses as well as postmortem tissue analysis concentrations from prescription opioid fatalities in children. We report a pediatric hydromorphone fatality with postmortem peripheral blood, central blood, liver, and gastric concentrations. CASE REPORT: A 3-year-old male was found unresponsive on a couch. Emergency services were contacted and responders found him pulseless, apneic, and asystolic. Resuscitative measures were unsuccessful and he was pronounced dead at a local hospital soon after arrival. Postmortem investigations revealed that two hydromorphone tablets (2 mg each) were missing. There was no demonstrable natural disease or traumatic injury to which to attribute his death upon autopsy; while postmortem concentrations of hydromorphone were confirmed and quantitated in peripheral blood at 0.03 mg/L, central blood 0.06 mg/L, and liver 0.10 mg/kg. CONCLUSION: Given the paucity of reported pediatric opioid-related fatalities, we describe a hydromorphonep-related death in a child, which includes postmortem hydromorphone concentrations.

A Fatality Related to Two Novel Hallucinogenic Compounds: 4-Methoxyphencyclidine and 4-Hydroxy-N-methyl-N-ethyltryptamine.

In this case report, we present an evaluation of postmortem concentration distribution of the hallucinogenic compound 4-methoxyphencyclidine (4-MeO-PCP) in a fatality principally attributed to this drug. Another hallucinogen, 4-hydroxy-N-methyl-N-ethyltryptamine was also detected, but was not quantitated. A man--who had a history of recent 'strange' behavior--was found deceased, on his bed, in his locked room. Toxicology testing, which initially screened positive for phencyclidine (PCP) by ELISA, subsequently detected and confirmed the two hallucinogens by gas chromatography-mass spectrometry. 4-MeO-PCP concentrations were then quantified by a specific secondary testing technique. The peripheral blood concentration was 8.2 mg/L compared with the central blood concentration of 14 mg/L. The liver concentration was 120 mg/kg, the vitreous was 5.1 mg/L, the urine was 140 mg/L and the gastric contents contained 280 mg. PCP was not detected, but therapeutic concentrations of venlafaxine, olanzapine, lorazepam and hydroxyzine were confirmed. The cause of death was certified due to acute mixed drug intoxication, and the manner of death was certified as accident.

Antemortem and postmortem methamphetamine blood concentrations: three case reports.

We compare antemortem whole-blood to postmortem peripheral blood concentrations of methamphetamine and its metabolite amphetamine in three medical examiner cases. Antemortem specimens, initially screened positive for methamphetamine by ELISA, were subsequently confirmed, together with the postmortem specimens, by GC-MS analysis following solid-phase extraction. Methamphetamine peripheral blood to antemortem blood ratios averaged 1.51 (± 0.049; n = 3) and amphetamine peripheral blood to antemortem blood ratios averaged 1.50 (n = 2). These data show that postmortem redistribution occurs for both methamphetamine and amphetamine, revealing that postmortem blood concentrations are ∼1.5 times greater than antemortem concentrations. Furthermore, as both methamphetamine and amphetamine have previously been shown to have liver/peripheral blood (L/P) ratios of 5-8, it can be proposed that drugs displaying L/P ratios ranging from 5 to 10 may exhibit postmortem concentrations up to twice those concentrations circulating in blood before death.

Fatal fluoxetine intoxication with markedly elevated central blood, vitreous, and liver concentrations.

Since being introduced into clinical practice 20 years ago, fluoxetine, a serotonin-reuptake inhibitor, has remained one of the most popular antidepressants prescribed in the United States. Upon reviewing the literature, the highest reported postmortem central blood fluoxetine and norfluoxetine concentrations are 22 and 6.8 mg/L, respectively, and reported liver fluoxetine and norfluoxetine concentrations are 29-128 and 17 mg/kg, respectively. A 31-year-old female with convulsive activity was found at home by her husband. Emergency services was contacted, and responders found the patient unresponsive with agonal respirations, a pulse of 20 bpm, and no measurable blood pressure. Despite all resuscitative efforts, the patient expired. Postmortem analyses revealed concentrations of 33 mg/L fluoxetine and 12 mg/L norfluoxetine in central blood and 400 mg/kg fluoxetine and 460 mg/kg norfluoxetine in liver. Vitreous fluoxetine and norfluoxetine concentrations were 5.2 and 2.2 mg/L, respectively. Utilizing a sensitive and specific analytical procedure, we report the highest recorded central blood and liver fluoxetine and norfluoxetine concentrations.