EC Clinical and Medical Case Reports

Sudden infant and childhood deaths are a catastrophic enigma since the cause is unexplained, even after careful investigation, and it remains a diagnosis of exclusion. It is proposed that febrile seizures may play a significant role in these deaths, and that a sudden spike in fever may be the initial manifestation of the seizure, which may be reflected by a rise in expression of heat shock protein. Further studies to confirm this observation and recognize structural, metabolic and genetic markers to identify those at risk are warranted. Special attention to assess risk following certain childhood vaccinations is also necessary. Even when medication to control fever is given, and the fever remains low-grade, a sudden spike in temperature can occur, which may be the first indication of seizure onset. If this observation is confirmed, an effective method to alert that a temperature spike is occurring is needed to facilitate rapid intervention of seizure control with rectal diazepam. The seizure may be sufficiently severe to cause death if untreated.

 Keywords: Sudden Infant Death Syndrome (SIDS); Febrile Seizure; Diazepam

1. Shapiro-Mendoza CK., et al. “Half century since SIDS: A reappraisal of terminology”. Pediatrics4 (2021): e2021053746.
2. Hesdorffer DC., et al. “Sudden unexplained death in childhood: a comparison of cases with and without febrile seizure history”. Epilepsia8 (2015): 1294-1300.
3. Hefti MM., et al. “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 Science, Medicine and Pathology 1 (2016): 4-13.
4. Devinsky O., et al. “Recognizing and preventing epilepsy-related mortality. A call for action”. Neurology8 (2016): 779-786.
5. Crandall L and Devinsky O. “Sudden unexplained death in children. Comment”. The Lancet Child and Adolescent Health 1 (2017): 8-9.
6. Crandall LG., et al. “Potential role of febrile seizures and other risk factors associated with sudden deaths in children”. JAMA Network Open 4 (2019): e192739.
7. Berg AT. “Are febrile seizures provoked by a rapid rise in temperature?” American Journal of Diseases of Children 10 (1993): 1101-1103.
8. Cohn DF., et al. “Thermal epilepsy manifest as fever attacks”. Annals of Internal Medicine 4 (1984): 569-570.
9. Wachtel TJ., et al. “Natural history of fever following seizure”. Archives of Internal Medicine 6 (1987): 1153-1155.
10. Febrile Seizures. NIH.NINCDS Publications. Last reviewed November 22, 2024.
11. Chan KM. “Epilepsy - Another cause of intermittent fever with confusion”. Postgraduate Medical Journal 796 (1992): 119-120.
12. Mosilin P., et al. “The pathogenesis of fever-induced febrile seizures and its current state”. Neuroscience Insights 15 (2020): 2633105520956973.
13. Iwasaki N., et al. “Molecular genetics of febrile seizures”. Epilepsia9 (2022): 32-35.
14. Gould L., et al. “Video analysis of sudden unexplained deaths in toddlers”. Neurology3 (2024): e208038.
15. Deng L., et al. “Seizures following vaccination in children. Risks, outcomes and management of subsequent revaccination”. American Journal of Geriatric Psychiatry 10 (2020): 644-649.
16. Sawires R., et al. “A review of febrile seizures: recent advances in understanding of febrile seizure pathophysiology and commonly implicated viral triggers”. Frontiers in Pediatrics 9 (2022): 801321.
17. McGuone D., et al. “Sudden unexplained death in childhood: A neuropathology review”. Frontiers in Neurology 11 (2020): 582061.
18. Moon RY., et al. “Evidence base for 2022 updated recommendations for a safe infant sleeping environment to reduce the risk of sleep-related infant deaths”. Pediatrics1 (2022): e2022057991.
19. Corsello A., et al. “Febrile seizures: A systematic review of different guidelines”. Pediatric Neurology 155 (2024): 141-148.
20. Sofijanov N., et al. “Febrile seizures: Clinical characteristics and initial EEG”. Epilepsia1 (1992): 52-57.
21. Berg AT and Shinnar S. “Complex febrile seizures”. Epilepsia2 (1996): 126-133.
22. Wilmshurst JM., et al. “Summary of recommendations for the management of infantile seizures: Task force report for the ILAE commission on pediatrics”. Epilepsia8 (2015): 1185-1198.
23. Ferretti A., et al. “Best practices for the management of febrile seizures in children”. Italian Journal Pediatrics1 (2024): 95.
24. Kon FC., et al. “Hippocampal abnormalities and seizures: A 16-year single center review of sudden unexpected death in childhood, sudden unexpected death in epilepsy and SIDS”. Forensic Science, Medicine and Pathology 3 (2020): 423-434.
25. Lewis DV., et al. “Hippocampal sclerosis and temporal lobe epilepsy following febrile status epilepticus: The FEBSTAT study”. Epilepsia6 (2024): 1568-1580.
26. Hefti MM., et al. “Hippocampal malformation with sudden death in early childhood: A neuropathological study: part 2 of the investigations of the San Diego SUDC research project”. Forensic Science, Medicine and Pathology 1 (2016): 14-25.
27. Koh HY., et al. “Genetic determinants of sudden unexpected death in pediatrics”. Genetics in Medicine4 (2022): 839-850.
28. Skotte L., et al. “Genome-wide association study of febrile seizures implicates fever response and neuronal excitability genes”. Brain2 (2022): 555-568.
29. Blitz S and Speltz L. “Febrile seizures”. Pediatric Annals10 (2023): e388-e393.
30. Devinsky O., et al. “Recognizing and preventing epilepsy-related mortality. A call for action”. Neurology8 (2016): 779-786.
31. Wojcik MH., et al. “Sudden unexplained death in childhood. current understanding”. Pediatric Emergency Care 12 (2023): 979-985.
32. Sinnar S., et al. “MRI abnormalities following febrile status epilepticus in children. The FEBSTAT Study”. Neurology 9 (2012): 871-877.
33. Das R., et al. “MRI abnormalities of the brain after complex febrile seizures in children”. Cureus12 (2022): e33084.
34. Murata S., et al. “Acetaminophen and febrile seizure recurrences during the same fever episode”. Pediatrics5 (2018): e20181009.
35. Inoue M., et al. “Change in the strategy for prophylactic diazepam and the impact on seizure recurrence within 24h. seizure”. European Journal of Epilepsy 75 (2020): 70-74.
36. Febrile Seizures and Vaccines. CDC Vaccine Safety (2024).