title: 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.
authors.affiliation: Department of Pathology (Neuropathology), Children's Hospital and Harvard Medical School, Enders Building, Room 1112, 300 Longwood Avenue, Boston, MA, 02115, USA. Hannah.kinney@childrens.harvard.edu
authors.forename: Hannah C
authors.initials: HC
authors.lastname: Kinney
authors.forename: Amy E
authors.initials: AE
authors.lastname: Chadwick
authors.forename: Laura A
authors.initials: LA
authors.lastname: Crandall
authors.forename: Marjorie
authors.initials: M
authors.lastname: Grafe
authors.forename: Dawna L
authors.initials: DL
authors.lastname: Armstrong
authors.forename: William J
authors.initials: WJ
authors.lastname: Kupsky
authors.forename: Felicia L
authors.initials: FL
authors.lastname: Trachtenberg
authors.forename: Henry F
authors.initials: HF
authors.lastname: Krous
mesh_terms: D002675:Child, Preschool; D003645:Death, Sudden / Q000209:etiology*; D005260:Female; D006624:Hippocampus / Q000002:abnormalities*; D006801:Humans; D007223:Infant; D008297:Male; D016684:Prone Position; D003294:Seizures, Febrile / Q000209:etiology*; D012890:Sleep; D013702:Temporal Lobe / Q000002:abnormalities*