Sudden Death, Febrile Seizures, and Hippocampal and Temporal Lobe Maldevelopment in Toddlers: A New Entity

Abstract

Recently, we reported hippocampal and temporal lobe abnormalities in 5 toddlers with sudden unexplained death in childhood (SUDC). The association of these anomalies with a high incidence (40%) of individual/ family histories of simple febrile seizures in the cases raised concern that febrile seizures can be associated with death. In a series of 64 toddlers with sudden death, we tested the hypothesis that an SUDC subset is characterized by hippocampal and temporal lobe maldevelopment and an individual and/or family history of simple familial seizures. Cases of sudden and unexplained death in children aged 1.0 to 5.9 years (median 1.7 years) were divided into groups based upon a history of febrile or nonfebrile seizures, familial febrile seizures, and autopsy classification of cause of death. Forty-nine of the 64 cases (77%) were classified as SUDC, of which 40% had an individual/family history of febrile seizures. Of the 26 SUDC cases with available hippocampal sections, 62% (16/26) had hippocampal and temporal lobe anomalies, including 82% (9/11) of cases with an individual/family history of febrile seizures. Cases with these anomalies were all found dead during a sleep period, typically in the prone (87%) position. We conclude that a potential new entity may account for the majority of SUDC in toddlers, defined by sleep-related death in the prone position, individual/family history of febrile seizures, and hippocampal and temporal lobe anomalies. The mechanism of death appears analogous to sudden death in (temporal lobe) epilepsy, with a putative unwitnessed seizure during sleep leading to airway occlusion and death. This study mandates further research into the potential link between simple febrile seizures and death.

Sudden unexplained death in childhood (1–4 years) in Ireland: an epidemiological profile and comparison with SIDS

“…The observation of a high incidence of a history of febrile seizures among SUDC relative to SIDS (<1%) and the general paediatric population (2–5%) is in agreement with previously published reports 23–26. Kinney et al described neuropathological abnormalities in the hippocampus and temporal lobe in a large proportion of SUDC 26.…”

“…Kinney et al described neuropathological abnormalities in the hippocampus and temporal lobe in a large proportion of SUDC 26. Many of these findings (including hippocampal sclerosis, gliosis and hippocampal asymmetry) are also seen in temporal lobe epilepsy and the authors postulated that a potential new entity may account for the majority of SUDC in toddlers, defined by sleep related death in the prone position, an individual/family history of febrile seizures and hippocampal anomalies.…”

The Structural Connectome of the Human Central Homeostatic Network

“…Medullary-forebrain connectivity through the human LFB also provides a potential neuroanatomic basis for CHN disorders such as SUDEP (Engel et al, 2013;Richardson, 2012;Sowers et al, 2013), which is associated with temporal lobe epilepsy (Mueller et al, 2014;Schuele et al, 2011), as well as SIDS and SUDC, which are associated with hippocampal anomalies in infants and young children, respectively (Kinney et al, 2007(Kinney et al, , 2009(Kinney et al, , 2015. A paradoxical feature of the CHN is its marked susceptibility to generate and propagate seizures (Harper, 1986;Oliveira et al, 2011)-paradoxical in that a network so vital to survival is so prone to seizures that are inherently dangerous and potentially lethal.…”

“…Furthermore, the concept of a CHN is based upon the recognition that the network regulates not only autonomic functions (i.e., cardiac muscle, smooth muscle, and sweat glands) but also respiratory functions, which are mediated by skeletal muscle. The CHN connectome identified in this study represents an initial step toward elucidating the neuroanatomy of human homeostasis and defining altered connectivity in future studies of patients with disorders of homeostasis, such as sudden infant death syndrome (SIDS) (Kinney et al, 2015), sudden unexplained death in childhood (SUDC) (Kinney et al, 2007(Kinney et al, , 2009, and sudden unexplained death in epilepsy (SUDEP) (Massey et al, 2014).…”

When your child with epilepsy die suddenly: febrile seizures are part of the process?

“…Corroborating this hypothesis, Kinney et al 32 demonstrated a high incidence of FS history in children that suffered of sudden death, not related to epilepsy. SUDEP is the most important direct epilepsy-related cause of death and while the exactly mechanisms or set of factors involved on SUDEP occurrence are still not clear the principal effort in preventing SUDEP should be prompt and optimal seizure control, especially generalized convulsive seizures and identification of cardiovascular associated diseases 33 .…”