An Association of Hippocampal Malformations and Sudden Death? We Need More Data

Ackerman, Michael J.; Andrew, Tom W.; Baker, Andrew; Devinsky, Orrin; Downs, James C.; Keens, Thomas G.; Kuntz, Joanne; Lin, Peter T.; Lear-Kaul, Kelly C.; Reichard, R. Ross; Robinson, Deborah A.

doi:10.1007/s12024-016-9765-1

Cited by 9 publications

(9 citation statements)

References 4 publications

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“…Hippocampal findings, particularly in the DG, are frequent in SUDC [9,10,14] and parallel findings in TLE [8,[10][11][12]. However, our small prospective study (n = 20) identified hippocampal findings in SUDC cases and cardiogenetic COD [2], which was similarly reported in other explained COD cases [3,9].…”

Section: Discussionsupporting

confidence: 84%

Blinded review of hippocampal neuropathology in sudden unexplained death in childhood reveals inconsistent observations and similarities to explained paediatric deaths

Leitner

McGuone

William

et al. 2021

Neuropathology Appl Neurobio

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Aims: Hippocampal findings are implicated in the pathogenesis of sudden unexplained death in childhood (SUDC), although some studies have identified similar findings in sudden explained death in childhood (SEDC) cases. We blindly reviewed hippocampal histology in SUDC and SEDC controls.Methods: Hippocampal haematoxylin and eosin (H&E) slides (n = 67; 36 SUDC, 31 controls) from clinical and forensic collaborators were evaluated by nine blinded reviewers: three board-certified forensic pathologists, three neuropathologists and three dual-certified neuropathologists/forensic pathologists.Results: Among nine reviewers, about 50% of hippocampal sections were rated as abnormal (52.5% SUDC, 53.0% controls), with no difference by cause of death (COD) (p = 0.16) or febrile seizure history (p = 0.90). There was little agreement among nine reviewers on whether a slide was within normal range (Fleiss' κ = 0.014, p = 0.47). Within reviewer [Correction added on 24 AUG 2021, after first online publication: Peer review history statement has been added.]

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Section: Discussionsupporting

confidence: 84%

Blinded review of hippocampal neuropathology in sudden unexplained death in childhood reveals inconsistent observations and similarities to explained paediatric deaths

Leitner

McGuone

William

et al. 2021

Neuropathology Appl Neurobio

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“…Malrotation of the hippocampus was found on MRI in 8.8% of patients with febrile status in the FEBSTAT study [72] with predilection for the left side, compared to 2.1% in their control groups [73]. Hippocampal malrotation may represent a substrate to febrile seizure and epilepsy [74] and granule cell dispersion is postulated as a morphological biomarker in SIDS that could indicate impaired connectivity between the hippocampus and brainstem [68] or a manifestation of previous unrecognised ictal activity [75]. Granule cell dispersion, a common and often prominent feature in approximately 40% of adult TLE patients with hippocampal sclerosis [34], was reported in only 4% of 145 SUDEP cases without sclerosis [31].…”

Section: Introductionmentioning

confidence: 99%

Review: The past, present and future challenges in epilepsy‐related and sudden deaths and biobanking

Thom¹,

Boldrini

Bundock

et al. 2018

Neuropathology Appl Neurobio

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The past, present and future challenges in epilepsy-related and sudden deaths and biobanking Awareness and research on epilepsy-related deaths (ERD), in particular Sudden Unexpected Death in Epilepsy (SUDEP), have exponentially increased over the last two decades. Most publications have focused on guidelines that inform clinicians dealing with these deaths, educating patients, potential risk factors and mechanisms. There is a relative paucity of information available for pathologists who conduct these autopsies regarding appropriate post mortem practice and investigations. As we move from recognizing SUDEP as the most common form of ERD toward indepth investigations into its causes and prevention, health professionals involved with these autopsies and post mortem procedure must remain fully informed.Systematizing a more comprehensive and consistent practice of examining these cases will facilitate (i) more precise determination of cause of death, (ii) identification of SUDEP for improved epidemiological surveillance (the first step for an intervention study), and (iii) biobanking and cell-based research. This article reviews how pathologists and healthcare professionals have approached ERD, current practices, logistical problems and areas to improve and harmonize. The main neuropathology, cardiac and genetic findings in SUDEP are outlined, providing a framework for best practices, integration of clinical, pathological and molecular genetic investigations in SUDEP, and ultimately prevention.

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“…Similar GCL alterations occur in hippocampal sclerosis in temporal lobe epilepsy, where FDGB is associated with more severe disease (44). Whether these changes are necessary or sufficient to cause seizures in SUDC remains unproven and controversial (16,45,46). Unlike temporal lobe epilepsy, hippocampal sclerosis is rare or never occurs in SUDC while acquired hippocampal injury (e.g., neuronal loss or gliosis) is uncommon in SUDC (13,15,16).…”

Section: Neuropathologic Findings In Sudcmentioning

confidence: 99%

“…Notably, almost half of the cohort did not have hippocampal alterations and 27% did not have febrile seizures. However, researchers have since raised concerns about the reliability of the association in the SDSRP study, as hippocampal tissue was unavailable for analysis in approximately half the cases (46). Other methodologic issues included an incomplete dataset populated by self-referred cases that lacked standardized death investigation, with frequent limited brain examination and sampling (46,55).…”

Section: Neuropathologic Findings In Sudcmentioning

confidence: 99%

Sudden Unexplained Death in Childhood: A Neuropathology Review

2020

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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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An Association of Hippocampal Malformations and Sudden Death? We Need More Data

Cited by 9 publications

References 4 publications

Blinded review of hippocampal neuropathology in sudden unexplained death in childhood reveals inconsistent observations and similarities to explained paediatric deaths

Blinded review of hippocampal neuropathology in sudden unexplained death in childhood reveals inconsistent observations and similarities to explained paediatric deaths

Review: The past, present and future challenges in epilepsy‐related and sudden deaths and biobanking

Sudden Unexplained Death in Childhood: A Neuropathology Review

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