scholarly journals Neuropathologic Changes in Sudden Unexplained Death in Childhood

2020 ◽  
Vol 79 (3) ◽  
pp. 336-346 ◽  
Author(s):  
Declan McGuone ◽  
Dominique Leitner ◽  
Christopher William ◽  
Arline Faustin ◽  
Nalin Leelatian ◽  
...  
Keyword(s):  
Granule Cells ◽  
Ex Vivo ◽  
Febrile Seizures ◽  
Common Finding ◽  
Molecular Testing ◽  
Sudden Unexplained Death ◽  
Unexplained Death ◽  
Autopsy Data ◽  
History Of ◽  
Hippocampal Alterations

Abstract Sudden unexplained death in childhood (SUDC) affects children >1-year-old whose cause of death remains unexplained following comprehensive case investigation and is often associated with hippocampal abnormalities. We prospectively performed systematic neuropathologic investigation in 20 SUDC cases, including (i) autopsy data and comprehensive ancillary testing, including molecular studies, (ii) ex vivo 3T MRI and extensive histologic brain samples, and (iii) blinded neuropathology review by 2 board-certified neuropathologists. There were 12 girls and 8 boys; median age at death was 33.3 months. Twelve had a history of febrile seizures, 85% died during apparent sleep and 80% in prone position. Molecular testing possibly explained 3 deaths and identified genetic mutations in TNNI3, RYR2, and multiple chromosomal aberrations. Hippocampal abnormalities most often affected the dentate gyrus (altered thickness, irregular configuration, and focal lack of granule cells), and had highest concordance between reviewers. Findings were identified with similar frequencies in cases with and without molecular findings. Number of seizures did not correlate with hippocampal findings. Hippocampal alterations were the most common finding on histological review but were also found in possibly explained deaths. The significance and specificity of hippocampal findings is unclear as they may result from seizures, contribute to seizure pathogenesis, or be an unrelated phenomenon.

scholarly journals Minimally invasive autopsy for fetuses and children based on a combination of post-mortem MRI and endoscopic examination: a feasibility study

2019 ◽  
Vol 23 (46) ◽  
pp. 1-104 ◽  
Author(s):  
Celine Lewis ◽  
John C Hutchinson ◽  
Megan Riddington ◽  
Melissa Hill ◽  
Owen J Arthurs ◽  
...  
Keyword(s):  
Minimally Invasive ◽  
Cause Of Death ◽  
Clinical Indication ◽  
Religious Leaders ◽  
Training Requirements ◽  
Less Invasive ◽  
Sudden Unexplained Death ◽  
Unexplained Death ◽  
Minimally Invasive Autopsy ◽  
Autopsy Data

BackgroundLess invasive perinatal and paediatric autopsy methods, such as imaging alongside targeted endoscopy and organ biopsy, may address declining consent rates for traditional autopsy, but their acceptability and accuracy are not known.ObjectivesThe aims of this study were to provide empirical data on the acceptability and likely uptake for different types of autopsy among key stakeholders (study 1); and to analyse existing autopsy data sources to provide estimates of the potential efficacy of less invasive autopsy (LIA) and its projected utility in clinical practice (study 2).Review methodsStudy 1: this was a mixed-methods study. Parents were involved in research design and interpretation of findings. Substudy 1: a cross-sectional survey of 859 parents who had experienced miscarriage, termination of pregnancy for fetal anomaly, stillbirth, infant or child death, and interviews with 20 responders. Substudy 2: interviews with 25 health professionals and four coroners. Substudy 3: interviews with 16 religious leaders and eight focus groups, with 76 members of the Muslim and Jewish community. Study 2: a retrospective analysis of national data in addition to detailed information from an existing in-house autopsy database of > 5000 clinical cases that had undergone standard autopsy to determine the proportion of cases by clinical indication group for which tissue sampling of specific internal organs significantly contributed to the diagnosis.ResultsSubstudy 1: 91% of participants indicated that they would consent to some form of LIA, 54% would consent to standard autopsy, 74% to minimally invasive autopsy (MIA) and 77% to non-invasive autopsy (NIA). Substudy 2: participants viewed LIA as a positive development, but had concerns around the limitations of the technology and de-skilling the workforce. Cost implications, skills and training requirements were identified as implementation challenges. Substudy 3: religious leaders agreed that NIA was religiously permissible, but MIA was considered less acceptable. Community members indicated that they might consent to NIA if the body could be returned for burial within 24 hours. Study 2: in 5–10% of cases of sudden unexplained death in childhood and sudden unexplained death in infants, the final cause of death is determined by routine histological sampling of macroscopically normal organs, predominantly the heart and lungs, and in this group routine histological sampling therefore remains an important aspect of investigation. In contrast, routine histological examination of macroscopically normal organs rarely (< 0.5%) provides the cause of death in fetal cases, making LIA and NIA approaches potentially highly applicable.LimitationsA key limitation of the empirical research is that it is hypothetical. Further research is required to determine actual uptake. Furthermore, because of the retrospective nature of the autopsy data set, findings regarding the likely contribution of organ sampling to final diagnosis are based on extrapolation of findings from historical autopsies, and prospective data collection is required to validate the conclusions.ConclusionsLIA is viable and acceptable (except for unexplained deaths), and likely to increase uptake. Further health economic, performance and implementation studies are required to determine the optimal service configuration required to offer this as routine clinical care.FundingThe National Institute for Health Research Health Technology Assessment programme.

scholarly journals Incidence and Etiology of Sudden Cardiac Death: New Updates for Athletic Departments

2017 ◽  
Vol 9 (3) ◽  
pp. 268-279 ◽  
Author(s):  
Irfan M. Asif ◽  
Kimberly G. Harmon
Keyword(s):  
African Americans ◽  
Sudden Cardiac Death ◽  
Cause Of Death ◽  
Cardiac Death ◽  
The United States ◽  
Common Finding ◽  
Normal Heart ◽  
Basketball Players ◽  
Sudden Unexplained Death ◽  
Unexplained Death

Context: Sudden cardiac death (SCD) in a young athlete is a tragic event and is the leading medical cause of death in this population. The precise incidence of SCD in young athletes has been subject of debate, with studies reporting drastically different rates (1:917,000 athlete-years (AYs) to 1:3000 AYs) depending on the methodological design of the investigation or the targeted population. Evidence Acquisition: A literature search was performed in PubMed using the terms: incidence, sudden cardiac death, sudden death, sudden cardiac arrest, etiology, pathology, registry, athlete, young, children, and adolescents. Articles were reviewed for relevance and included if they contained information on the incidence of SCD in athletes or young persons up to the age of 35 years. Study Design: Clinical review. Level of Evidence: Level 5. Results: Studies of high quality and rigor consistently yield an incidence of 1:50,000 AYs in college athletes and between 1:50,000 and 1:80,000 AYs for high school athletes, with certain subgroups that appear to be at particularly high risk, including the following: men, basketball players, and African Americans. Initial reports suggest that the most common cause of SCD is hypertrophic cardiomyopathy (HCM). However, more comprehensive investigations in the United States and international populations—athletes, nonathletes, and military—support that the most common finding on autopsy in young individuals with SCD is actually a structurally normal heart (autopsy-negative sudden unexplained death). Conclusion: SCD is the leading cause of death in athletes during exercise and usually results from intrinsic cardiac conditions that are triggered by the physiologic demands of vigorous exercise. Current rates of SCD appear to be at least 4 to 5 times higher than previously estimated, with men, African Americans, and male basketball players being at greatest risk. Emerging data suggest that the leading finding associated with SCD in athletes is actually a structurally normal heart (autopsy-negative sudden unexplained death).

scholarly journals Inheritance of Febrile Seizures in Sudden Unexplained Death in Toddlers

2012 ◽  
Vol 46 (4) ◽  
pp. 235-239 ◽  
Author(s):  
Ingrid A. Holm ◽  
Annapurna Poduri ◽  
Laura Crandall ◽  
Elisabeth Haas ◽  
Marjorie R. Grafe ◽  
...  
Keyword(s):  
Febrile Seizures ◽  
Sudden Unexplained Death ◽  
Unexplained Death

scholarly journals Sustained Opening of the Blood-Brain Barrier with Progressive Accumulation of White Matter Hyperintensities Following Ischemic Stroke

2019 ◽  
Vol 9 (1) ◽  
pp. 16 ◽  
Author(s):  
Imama Naqvi ◽  
Emi Hitomi ◽  
Richard Leigh
Keyword(s):  
Ischemic Stroke ◽  
White Matter ◽  
Acute Stroke ◽  
Blood Brain Barrier ◽  
White Matter Hyperintensities ◽  
Brain Barrier ◽  
Common Finding ◽  
Blood Brain ◽  
History Of ◽  
Iv Tpa

Objective: To report a patient in whom an acute ischemic stroke precipitated chronic blood-brain barrier (BBB) disruption and expansion of vascular white matter hyperintensities (WMH) into regions of normal appearing white matter (NAWM) during the following year. Background: WMH are a common finding in patients with vascular risk factors such as a history of stroke. The pathophysiology of WMH is not fully understood; however, there is growing evidence to suggest that the development of WMH may be preceded by the BBB disruption in the NAWM. Methods: We studied a patient enrolled in the National Institutes of Health Natural History of Stroke Study who was scanned with magnetic resonance imaging (MRI) after presenting to the emergency room with an acute stroke. After a treatment with IV tPA, she underwent further MRI scanning at 2 h, 24 h, 5 days, 30 days, 90 days, 6 months, and 1-year post stroke. BBB permeability images were generated from the perfusion weighted imaging (PWI) source images. MRIs from each time point were co-registered to track changes in BBB disruption and WMH over time. Results: An 84-year-old woman presented after acute onset right hemiparesis, right-sided numbness and aphasia with an initial NIHSS of 13. MRI showed diffusion restriction in the left frontal lobe and decreased blood flow on perfusion imaging. Fluid attenuated inversion recovery (FLAIR) imaging showed bilateral confluent WMH involving the deep white matter and periventricular regions. She was treated with IV tPA without complication and her NIHSS improved initially to 3 and ultimately to 0. Permeability maps identified multiple regions of chronic BBB disruption remote from the acute stroke, predominantly spanning the junction of WMH and NAWM. The severity of BBB disruption was greatest at 24 h after the stroke but persisted on subsequent MRI scans. Progression of WMH into NAWM over the year of observation was detected bilaterally but was most dramatic in the regions adjacent to the initial stroke. Conclusions: WMH-associated BBB disruption may be exacerbated by an acute stroke, even in the contralateral hemisphere, and can persist for months after the initial event. Transformation of NAWM to WMH may be evident in areas of BBB disruption within a year after the stroke. Further studies are needed to investigate the relationship between chronic BBB disruption and progressive WMH in patients with a history of cerebrovascular disease and the potential for acute stroke to trigger or exacerbate the process leading to the development of WMH.

scholarly journals No evidence of false-negative Plasmodium falciparum rapid diagnostic results in Monrovia, Liberia

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Mandella King ◽  
Alexander E. George ◽  
Pau Cisteró ◽  
Christine K. Tarr-Attia ◽  
Beatriz Arregui ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
False Negative ◽  
Malaria Diagnosis ◽  
Rapid Diagnostic Tests ◽  
Molecular Testing ◽  
False Negatives ◽  
Gene Deletions ◽  
History Of ◽  
Catholic Hospital ◽  
Or History

Abstract Background Malaria diagnosis in many malaria-endemic countries relies mainly on the use of rapid diagnostic tests (RDTs). The majority of commercial RDTs used in Africa detect the Plasmodium falciparum histidine-rich protein 2 (PfHRP2). pfhrp2/3 gene deletions can therefore lead to false-negative RDT results. This study aimed to evaluate the frequency of PCR-confirmed, false-negative P. falciparum RDT results in Monrovia, Liberia. Methods PfHRP2-based RDT (Paracheck Pf®) and microscopy results from 1038 individuals with fever or history of fever (n = 951) and pregnant women at first antenatal care (ANC) visit (n = 87) enrolled in the Saint Joseph’s Catholic Hospital (Monrovia) from March to July 2019 were used to assess the frequency of false-negative RDT results. True–false negatives were confirmed by detecting the presence of P. falciparum DNA by quantitative PCR in samples from individuals with discrepant RDT and microscopy results. Samples that were positive by 18S rRNA qPCR but negative by PfHRP2-RDT were subjected to multiplex qPCR assay for detection of pfhrp2 and pfhrp3. Results One-hundred and eighty-six (19.6%) and 200 (21.0%) of the 951 febrile participants had a P. falciparum-positive result by RDT and microscopy, respectively. Positivity rate increased with age and the reporting of joint pain, chills and shivers, vomiting and weakness, and decreased with the presence of coughs and nausea. The positivity rate at first ANC visit was 5.7% (n = 5) and 8% (n = 7) by RDT and microscopy, respectively. Out of 207 Plasmodium infections detected by microscopy, 22 (11%) were negative by RDT. qPCR confirmed absence of P. falciparum DNA in the 16 RDT-negative but microscopy-positive samples which were available for molecular testing. Among the 14 samples that were positive by qPCR but negative by RDT and microscopy, 3 only amplified pfldh, and among these 3 all were positive for pfhrp2 and pfhrp3. Conclusion There is no qPCR-confirmed evidence of false-negative RDT results due to pfhrp2/pfhrp3 deletions in this study conducted in Monrovia (Liberia). This indicates that these deletions are not expected to affect the performance of PfHRP2-based RDTs for the diagnosis of malaria in Liberia. Nevertheless, active surveillance for the emergence of PfHRP2 deletions is required.

scholarly journals Differential Methylation in the GSTT1 Regulatory Region in Sudden Unexplained Death and Sudden Unexpected Death in Epilepsy

2021 ◽  
Vol 22 (6) ◽  
pp. 2790
Author(s):  
Steffan Noe Christiansen ◽  
Stine Bøttcher Jacobsen ◽  
Jeppe Dyrberg Andersen ◽  
Marie-Louise Kampmann ◽  
Linea Christine Trudsø ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cardiac Tissue ◽  
Heart Diseases ◽  
Regulatory Region ◽  
Differential Methylation ◽  
Sudden Unexpected Death ◽  
Diagnostic Challenge ◽  
Unexpected Death ◽  
Sudden Unexplained Death ◽  
Unexplained Death

Sudden cardiac death (SCD) is a diagnostic challenge in forensic medicine. In a relatively large proportion of the SCDs, the deaths remain unexplained after autopsy. This challenge is likely caused by unknown disease mechanisms. Changes in DNA methylation have been associated with several heart diseases, but the role of DNA methylation in SCD is unknown. In this study, we investigated DNA methylation in two SCD subtypes, sudden unexplained death (SUD) and sudden unexpected death in epilepsy (SUDEP). We assessed DNA methylation of more than 850,000 positions in cardiac tissue from nine SUD and 14 SUDEP cases using the Illumina Infinium MethylationEPIC BeadChip. In total, six differently methylated regions (DMRs) between the SUD and SUDEP cases were identified. The DMRs were located in proximity to or overlapping genes encoding proteins that are a part of the glutathione S-transferase (GST) superfamily. Whole genome sequencing (WGS) showed that the DNA methylation alterations were not caused by genetic changes, while whole transcriptome sequencing (WTS) showed that DNA methylation was associated with expression levels of the GSTT1 gene. In conclusion, our results indicate that cardiac DNA methylation is similar in SUD and SUDEP, but with regional differential methylation in proximity to GST genes.

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