Published Research

The following research was made possible by the support of the SUDC Foundation.

Publications Related to SUDC

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2020

McGuone D, Leitner D, William C et al. Neuropathologic Changes in Sudden Unexplained Death in Childhood. Journal of Neuropathology & Experimental Neurology. 2020;79(3):336-346. doi:10.1093/jnen/nlz136

Authors prospectively performed systematic neuropathologic investigation in 20 SUDC cases and found hippocampal alterations were the most common finding on histological review but were also found in possibly explained deaths. They concluded the “significance and specificity of hippocampal findings is unclear as they may result from seizures, contribute to seizure pathogenesis, or be an unrelated phenomenon”.
Neuropathologic Changes in Sudden Unexplained Death in Childhood
https://doi.org/10.1093/jnen/nlz136

2019

National Association of Medical Examiners Panel on Sudden Unexpected Death in Pediatrics. Unexplained Pediatric Deaths: Investigation, Certification, and Family Needs. Bundock E, Corey T, editors. San Diego: Academic Forensic Pathology International; c2019. 340 p.

A combined effort of a panel of medical examiners, pediatricians, and federal agency representatives, representing the diverse interests of death investigation, autopsy performance, certification, clinical subspecialties (pediatrics, neurology, cardiology, child abuse, injury prevention, infectious diseases, genetics, and metabolic diseases), family needs, prevention, and epidemiology, culminated in this publication. Procedural guidance for investigation, autopsy and ancillary testing, certification and reporting, and key considerations for prevention, research and working with family members and other professional team members are provided.
www.sudpeds.com

Phoon C, Halvorsen M, Goldstein D et al. Sudden unexpected death in asymptomatic infants due to PPA2 variants. Mol Genet Genomic Med. 2019;8(1). doi:10.1002/mgg3.1008

Authors report two asymptomatic siblings who died unexpectedly at approximately 1 year of age found to have biallelic (compound heterozygous) variants in PPA2. PPA2 encodes a mitochondrially located inorganic pyrophosphatase implicated in progressive and lethal cardiomyopathies. Authors conclude these findings provide further information on clinical and molecular features of PPA2 variants.
Sudden Unexpected Death in Asymptomatic Infants Due to PPA2 Variants

OSAC, Proposed Standard Organizational and Foundational: Standard for Medicolegal Death Investigation, Prepared by Medicolegal Death Investigation Subcommittee Submitted to Standard Development Organization August 2019- Currently Under Review

The OSAC’s subcommittee on medicolegal death investigation has created and submitted to a standard development organization that describes the fundamental activities, minimal requirements, procedures, and personnel that are necessary to meet the basic components of a fully competent medicolegal death investigation system.

Crandall L, Lee J, Stainman R, Friedman D, Devinsky O. Potential Role of Febrile Seizures and Other Risk Factors Associated With Sudden Deaths in Children. JAMA Netw Open. 2019;2(4):e192739. doi:10.1001/jamanetworkopen.2019.2739

A case series study of 622 consecutive sudden child death cases aged 1 to 17 years from 2001 to 2017 from 18 countries reported to the SUDC Foundation. 391 families with child deaths aged 1 to 6 years with completed interviews were analyzed. “This analysis of the largest SUDC cohort confirmed an increased FS rate and found significantly increased rates of FS among sudden explained deaths in children. This study suggests that seizures may contribute to some SUDC and SEDC deaths. The risk of sudden death in a sibling was low. To develop and assess preventive strategies, population-based studies are needed to define the epidemiology and spectrum of risk factors and identify biomarkers of patients with FS at high risk of sudden death.”
Potential Role of Febrile Seizures and Other Risk Factors Associated with Sudden Deaths in Children

Goldstein RD1, Blair PS2, Sens MA3, Shapiro-Mendoza CK4, Krous HF5, Rognum TO6, Moon RY7; 3rd International Congress on Sudden Infant and Child Death. 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. Forensic Sci Med Pathol. 2019 Dec;15(4):622-628. doi: 10.1007/s12024-019-00156-9. Epub 2019 Sep 9. PMID: 31502215 PMCID: PMC6872710 [Available on 2020-12-01] DOI: 10.1007/s12024-019-00156-9

“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. Four categories (International Classification of Diseases (ICD)-11 categories of MH11, MH12, MH14, PB00-PB0Z) were recommended for classification, and explicit definitions and guidance were provided for death certifiers. A distinct category for children over the age of 1 was recommended (MH12). The conclusions will be submitted to the World Health Organization for inclusion in the upcoming ICD-11.”
Inconsistent Classification of Unexplained Sudden Deaths in Infants and Children Hinders Surveillance, Prevention and Research
https://doi.org/10.1007/s12024-019-00156-9

Hoch M, Bruno M, Faustin A et al. 3T MRI Whole-Brain Microscopy Discrimination of Subcortical Anatomy, Part 2: Basal Forebrain. American Journal of Neuroradiology. 2019;40(7):1095-1105. doi:10.3174/ajnr.a6088 (SUDCRRC)

Authors analyzed neuroimaging (3T MRI imaging scanner) data of the basal forebrain in SUDC cases and authors conclude findings “better define individual variations relevant to functional neurosurgical targeting and validate/complement advanced MR imaging methods”.

Hoch M, Bruno M, Faustin A et al. 3T MRI Whole-Brain Microscopy Discrimination of Subcortical Anatomy, Part 1: Brain Stem. American Journal of Neuroradiology. 2019. doi:10.3174/ajnr.a5956 (SUDCRRC)

Authors analyzed neuroimaging (3T MRI imaging scanner) data from SUDC cases of the brain stem which contains life-sustaining sensorimotor and autonomic structures. “Possible structure-function asymmetries in these pathways will require further study-that is, the cross-sectional area of the left corticospinal tract in the midpons appeared 20% larger (n = 13 brains, P < .10).”

2017

Crandall L, Devinsky O. Sudden unexplained death in children. Lancet Child Adolesc Health. 2017;1(1):8-9. doi:10.1016/s2352-4642(17)30003-2

A commentary by Laura Gould Crandall and Dr Devinsky on SUDC as an ignored public health issue.
Sudden Unexplained Death in Children

Gould Crandall L. Inexplicable Child Deaths: Medicolegal Death Investigation Resources from the SUDC Foundation and the SUDC Registry and Research Collaborative. Acad Forensic Pathol. 2017;7(2):xxiv-xxvi. doi:10.1177/192536211700700205

A review of resources available to the medicolegal death investigation community through the SUDC Foundation and NYU Langone Health’s SUDC Registry and Research Collaborative.
Inexplicable Child Deaths

Gould Crandall L, Reno L, Himes B, Robinson D. The Diagnostic Shift of SIDS to Undetermined: Are There Unintended Consequences? Acad Forensic Pathol. 2017 7(2): 212-220 PMID: 31239975 PMCID: PMC6474538 DOI: 10.23907/2017.022

Authors surveyed bereavement organization and bereaved parents to understand their perceptions of changing practices in regards to shifts in diagnoses of sudden infant death- including the use of SIDS, undetermined and asphyxia. Over 50% (34/67) of the organizations perceived the changing practices as effecting their ability to provide bereavement support and education. Forty percent (22/55) of parent stated they did not understand the final diagnosis of their infant's death. Author recommendations include the integration of collaborative efforts to combat sudden infant death with all stakeholders, in and outside of MDI, to achieve better understanding and eradication of these tragedies, improved public education, and effective care of all bereaved.
The Diagnostic Shift of SIDS to Undetermined

2016

OSAC Research and Development Needs: Pediatric Forensic Pathology to Improve the Accuracy of Cause and Manner of Death Certification, National Institute of Standards and Development, 2016

OSAC informs the forensic science community of research needs that are uncovered during standards development activities. The subcommittee on medicolegal death investigation issued a research need regarding pediatric sudden deaths. https://www.nist.gov/topics/organization-scientific-area-committees-forensic-science/osac-research-and-development-needs

Ackerman MJ1, Andrew TA2, Baker AM3, Devinsky O4, Downs JC5, Keens T6, Kuntz J7, Lin P1, Lear-Kaul KC8, Reichard R1, Robinson DA9. An Association of Hippocampal Malformations and Sudden Death? We Need More Data. Forensic Sci Med Pathol. 2016 Jun;12(2):229-31. doi: 10.1007/s12024-016-9765-1. Epub 2016 Mar 26.

The SUDC Scientific Advisory Board’s letter to the editor on the Hefti et al articles Part 1 and Part 2 describing the limitations of the study and the importance of “needing more data” and comprehensive investigations to understand the significance of stated hippocampal findings. The authors noted that such findings could be the cause or result of seizures, or non-related entity.

Hefti MM1,2,3, Cryan JB4, Haas EA5, Chadwick AE5, Crandall LA6, Trachtenberg FL7, Armstrong DD8, Grafe M9, Krous HF10, Kinney HC4. Hippocampal malformation associated with sudden death in early childhood: a neuropathologic study: Part 2 of the investigations of The San Diego SUDC Research Project. Forensic Sci Med Pathol. 2016 Mar;12(1):14-25. doi: 10.1007/s12024-015-9731-3. Epub 2016 Jan 19.

Authors detail the hippocampal findings in 42 cases from the San Diego SUDC Research Project. Key features described were focal granule cell bilamination of the dentate gyrus, and increased frequencies of other developmental abnormalities. Authors considered these changes a distinct clinicopathologic entity characterized by a likely developmental failure of neuronal migration in the dentate gyrus and that future research was needed to determine a causal role in sudden death.

Hefti MM, Kinney HC, Cryan JB, Haas EA, Chadwick AE, Crandall LA, Trachtenberg FL, Armstrong DD, Grafe M, Krous HF. 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 Forensic Sci Med Pathol. 2016 Mar;12(1):4-13. doi: 10.1007/s12024-015-9724-2. Epub 2016 Jan 19. PMID: 26782961

Data analysis of 151 cases of sudden unexpected childhood death collected retrospectively through the San Diego SUDC Research Project of which 80% (121/151) were subclassified as SUDC. Authors highlight findings in the hippocampus, a history of febrile seizures, relation to sleep and the roles of cardiac channelopathies and infections in causing sudden unexpected death in childhood. They reiterate the need for improved investigations.

NATIONAL COMMISSION ON FORENSIC SCIENCE, Views of the Commission: Recommendation on Formation of a National Office for Medicolegal Death Investigation. National Institute of Standards and Technology. U.S. Department of Commerce (Adopted at NCFS Meeting #11 - September 13, 2016)

National Commission on Forensic Science reports their view that the Attorney General should work to develop a permanent National Office of Medicolegal Death Investigation that would coordinate ongoing support of the nation’s medicolegal death investigation systems to improve quality, consistency, and the meeting of criminal justice and public health needs.

NATIONAL COMMISSION ON FORENSIC SCIENCE, Views of the Commission: Views on Communication with Next of Kin and Other Family Members. National Institute of Standards and Technology. U.S. Department of Commerce. Approved: September 16, 2016

Medicolegal death investigation is a public service, and conveying information in a clear, sensitive, and effective manner to the surviving family members is a critical aspect of the medicolegal death investigation system. It is the view of the National Commission on Forensic Science (NCFS) that: coroners and medical examiners should have policies to support sensitive interactions, to understand what translation and interpretation services are available and that professionals who interact with families should receive culturally competent appropriate training for communicating with the acutely bereaved.

2015

Hesdorffer DC, Crandall LA, Friedman D, Devinsky O; Sudden unexplained death in childhood: A comparison of cases with and without a febrile seizure history. Epilepsia. 2015 Aug;56(8):1294-300. doi: 10.1111/epi.13066. Epub 2015 Jun 29

Authors analyzed data of 123 consecutive children with SUDC reported to the SUDC program (4/1/11-3/31/14) by their parents and report that “31.7% of SUDC cases had a history of FS, among which 74.4% had simple FS. Compared to those without a history of FS, a history of FS was associated with a greater median age at death (p = 0.03) and death during the weekdays (p = 0.02). Terminal fever was similar in those with and without FS. The median time from FS to death was 6.0 months (interquartile range [IQR] 3.0-10.0). In all SUDC cases, prone position at death, death during sleep, and unwitnessed deaths predominated. There are parallels among SUDC, sudden infant deaths, and sudden unexpected death in epilepsy (SUDEP) with regard to prone position, unwitnessed deaths mostly during sleep, and male predominance. The greater than expected prevalence of a FS history and the proportion with terminal fever or illness in this cohort suggests that some SUDC deaths may be seizure related and therefore have potential commonalities with SUDEP.”

Halvorsen M, Petrovski S, Shellhaas R et al. Mosaic mutations in early-onset genetic diseases. Genetics in Medicine. 2015;18(7):746-749. doi:10.1038/gim.2015.155 (SUDCRRC)

Authors present an approach assessing frequently missed post-zygotic "mosaic" genetic mutations (those present in only a portion of the healthy parents' cells and are transmitted to offspring). It was applied 9 cases of sudden unexplained death in childhood (SUDC) and found a likely disease-causing mosaic mutation in an SCN1A mutation transmitted to an SUDC proband and her sibling with Dravet syndrome.

NATIONAL COMMISSION ON FORENSIC SCIENCE, Views on Increasing the Number, Retention, and Quality of Board-Certified Forensic Pathologists National Institute of Standards and Technology. U.S. Department of Commerce (Adopted at NCFS Meeting #7 – August 10-11, 2015)

This report reviews the reasons for the shortage of forensic pathologists and makes recommendations to increase their supply in the United States.

2014

Creation of NYU Langone’s SUDC Registry and Research Collaborative

SUDC Foundation founded (evolved from SUDC Program)

Rudd R, Capizzi Marain L, Crandall L To Hold or Not to Hold: Medicolegal Death Investigation Practices During Unexpected Child Death Investigations and the Experiences of Next of Kin. Am J Forensic Med Pathol. 2014 Jun;35(2):132-9 DOI: 10.1097/PAF.0000000000000089

197 professionals and 156 bereaved parents were surveyed regarding death investigation practices and experiences. Results showed that the majority of professional respondents (96.5%) allow the next of kin (NOK) to view his/her child before transport to the morgue while holding the infant/child was somewhat less commonplace (68.9%). The majority of professional respondents (70.4%) would also permit memorial keepsakes to be made. Furthermore, professional practices and NOK experiences in regard to communicating preliminary and final cause of death information to the NOK were highly variable.

Scientific Working Group for Medicolegal Death Investigation, Certification of Medicolegal Death Investigation Personnel- A Report and Recommendations. SWGMDI operated with support from National Institute of Justice through an Interagency agreement with FBI. (June 5, 2014)

SWGMDI recommends that all primary personnel responsible for investigating deaths, and the consultants and entities providing supportive services, be certified by a qualified accrediting agency.

Scientific Working Group for Medicolegal Death Investigation, Report and Recommendations for Research in Forensic Pathology/Medicolegal Death Investigation. SWGMDI operated with support from National Institute of Justice through an Interagency agreement with FBI. (Published June 5, 2014) www.swgmdi.org

SWGMDI identified barriers to research in medicolegal death investigation including time constraints, access to appropriate study materials, legal issues, skill, funding, obstacles encountered in writing grants, and lack of interest. They also provide recommendations to address barriers.

2013

Scientific Working Group for Medicolegal Death Investigation, Standards for Interactions Between Medical Examiner/Coroner Offices and Organ and Tissue Procurement Organizations and Eye Banks. SWGMDI operated with support from National Institute of Justice through an Interagency agreement with FBI. (Published June 20, 2013) www.swgmdi.org

SWGMDI provides standards to ensure appropriate interactions to support the donation of organs and tissues. It is the position of SWGMDI that “the procurement of at least some organs and/or tissues for transplantation can occur in almost all cases without a negative impact to the goals of medicolegal death investigation.”

Scientific Working Group for Medicolegal Death Investigation, Status of and Perceived Need for Regional Medicolegal Death Investigation Centers: A Report and Recommendations. SWGMDI operated with support from National Institute of Justice through an Interagency agreement with FBI. (Published July 19, 2013) www.swgmdi.org

SWGMDI evaluated the perceived need of regional medicolegal death investigation centers to meet the public needs.

2012

Ingrid A. Holm MD, MPH, Annapurna Poduri MD, MPH, Laura Crandall PT, MA, Elisabeth Haas MPH, Marjorie R. Grafe MD, PhD, Hannah C. Kinney MD, Henry F. Krous MD, Inheritance of Febrile Seizures in Sudden Unexplained Death in Toddlers. Pediatric Neurology 46 (2012) 235e239 DOI: 10.1016/j.pediatrneurol.2012.02.007

In this series, the major pattern of inheritance in toddlers with sudden unexplained death and febrile seizures was autosomal dominant. The authors recommend future studies to develop markers (including genetic) to identify which patients with febrile seizures are at risk for sudden death.

Kinney HC1, Rognum TO, Nattie EE, Haddad GG, Hyma B, McEntire B, Paterson DS, Crandall L, Byard RW. Sudden and unexpected death in early life: proceedings of a symposium in honor of Dr. Henry F. Krous. Forensic Sci Med Pathol. 2012 Dec;8(4):414-25. doi: 10.1007/s12024-012-9376-4.

Reported here are the proceedings of a symposium given in honor of Dr. Henry F. Krous upon his retirement of his distinguished 37-year-career dedicated to research into sudden unexpected death in infancy and childhood.

Scientific Working Group for Medicolegal Death Investigation (SWGMDI), Principles for Communicating with Next of Kin During Medicolegal Death Investigations. SWGMDI operated with support from National Institute of Justice through an Interagency agreement with FBI. (June 13, 2012) www.swgmdi.org

SWGMDI provides the 13 principles for professionals communicating with surviving families members during medicolegal death investigations. The authors explain that “families of individuals who died in situations requiring an investigation experience additional challenges and emotions not faced by families following normal or anticipated deaths. Sudden deaths exacerbate the experience of grief and loss- regardless of the manner of death. How medicolegal professionals communicate with families in the aftermath of a death will have a direct impact on their ability to cope, their view of the medicolegal system, and their willingness to cooperate with the investigation and future proceedings.”

Scientific Working Group for Medicolegal Death Investigation (SWGMDI), Guidelines for Media Relations - Dissemination of Public Information in Medicolegal Death Investigations. SWGMDI operated with support from National Institute of Justice through an Interagency agreement with FBI. (March 8, 2012) www.swgmdi.org

SWGMDI provides guidance on media relations related to medicolegal death investigations, including but not limited to information that MAY be released to the public and information that should NOT be released unless authorized.

Scientific Working Group for Medicolegal Death Investigation, Increasing the Supply of Forensic Pathologists in the United States: A Report and Recommendations. SWGMDI operated with support from National Institute of Justice through an Interagency agreement with FBI. www.swgmdi.org (Published December 5, 2012)

SWGMDI analyzed the shortage of forensic pathologists, provided background information on the problem, and offered ten recommendations to increase the supply of forensic pathologists in the United States to meet the needs of the public.

2009

Hannah C. Kinney, M.D., Amy E. Chadwick, B.A., Laura A. Crandall, M.A., Marjorie Grafe, M.D., Dawna L. Armstrong, M.D., William J. Kupsky, M.D., Felicia L. Trachtenberg, Ph.D., and Henry F. Krous, M.D. Sudden Death, Febrile Seizures, and Hippocampal and Temporal Lobe Maldevelopment in Toddlers: A New Entity Pediatr Dev Pathol 2009 Jul 16:1. DOI: 10.2350/08-09-0542.1

26 SUDC cases with available hippocampal sections, 62% (16/26) had hippocampal and temporal lobe anomalies. Authors conclude potential new entity defined by sleep-related death in prone position, with individual/family history of febrile seizures, and hippocampal and temporal lobe anomalies. This study mandates further research into the potential link between simple febrile seizures and death.

Baker AM, Crandall L. To Hold Or Not To Hold. Forensic Sci Med Pathol. 2009 (Dec; 5(4):321-3.

Dr Baker and Ms Crandall write a commentary discussing the pathologist versus family perspectives in death scene investigations. The authors conclude, “in the majority of situations—and certainly whenever possible—the family should be allowed a reasonable amount of time to touch and hold their child, managed in a way that does not hamper the investigation process.”

2007

Kinney HC, Armstrong DL, Chadwick AE, et al. Sudden Death in Toddlers Associated with Developmental Abnormalities of the Hippocampus: a report of five cases. Pediatr Dev Pathol. 2007;10:208-223 DOI: 10.2350/06-08-0144.1

Case report of 5 cases of SUDC in toddlers that we believe define a new entity associated with hippocampal anomalies at autopsy. Authors suggest risk factors include a case and/or family history of febrile seizures and recommend future studies to confirm and further evaluate findings.

Krous H, Chadwick A, Miller D, Crandall L, Kinney H. Sudden Death in Toddlers with Viral Meningitis, Massive Cerebral Edema, and Neurogenic Pulmonary Edema and Hemorrhage: Report of Two Cases. Pediatr Dev Pathol. 2007;10:463-469 DOI: 10.2350/06-08-0156.1

Case report of 2 sudden deaths in toddlers with clinical evidence of a viral infection and found at autopsy to have lymphocytic meningitis. Viral (lymphocytic) meningitis typically does not cause sudden death. Authors recommend the importance of a comprehensive autopsy, including detailed neuropathologic examination and viral testing, in determining of the cause of unexpected death in toddlers.

Masoumi H, Kinney HC, Chadwick AE, Rubio A, Krous HF. Sudden unexpected death in childhood associated with cardiac rhabdomyoma, involuting adrenal ganglioneuroma, and megalencephaly: another expression of tuberous sclerosis? Pediatr Dev Pathol. 2007;10:129-133. DOI: 10.2350/06-04-0081.1

A case report of a 9-year-old, previously healthy girl who died suddenly and unexpectedly and was found at postmortem examination to have a cardiac rhabdomyoma, megalencephaly, and an involuting adrenal ganglioneuroma. The authors suggest a possible diagnosis of tuberous sclerosis, but confirmatory genetic analysis was not performed.

2005

Krous HF, Chadwick AE, Crandall L, Nadeau-Manning. Sudden Unexpected Death In Childhood: A Report of 50 Cases. Pediatric Dev Pathol. 2005;8:307-319 DOI: 10.1007/s10024-005-1155-8

The first published definition of SUDC describing a profile characterized as male, 1 to 3 years in age, predominantly male, frequently personal and family history of seizures, and being found prone. The authors recommend legislation enabling research and formation of a multicenter research team to unravel the mystery of SUDC.

Wixom C, Krous HF, Chadwick AE. Sudden, Unexpected Death Associated with Meningioangiomatosis. Pediatr Dev Pathol. 2005;8:240-244 DOI: 10.1007/s10024-004-9105-4

A case report of a 13-year-old, previously healthy male without a history of seizures, neurologic deficits, or clinical stigmata of neurofibromatosis or family history. The autopsy revealed a brain mass descriptive of meningioangiomatosis (type of mass in/around meninges). The authors speculate his death was the result of a seizure due to meningioangiomatosis.

Krous HF1, Chadwick AE, Isaacs H Jr., Tumors associated with sudden infant and childhood death. Pediatr Dev Pathol. 2005 Jan-Feb;8(1):20-5. DOI: 10.1007/s10024-004-7077-z

A review of tumors associated with sudden infant and child death find they are rare but most (84%) affect the heart and brain and require thorough postmortem examination for accurate determination.

2001

Creation of the SUDC Program