October 19, 2023

CURE Epilepsy Discovery: Leading the Charge on Research and Awareness of Sudden Unexpected Death in Epilepsy (SUDEP)

Key Points

  • Sudden Unexpected Death in Epilepsy (SUDEP) is a tragic outcome defined by premature death in people with epilepsy that is not caused by drowning, injury, or other known causes of mortality.
  • CURE Epilepsy has been a leader in driving awareness and research on SUDEP since 2004, when it started the first private research program to investigate SUDEP and its prevention.
  • CURE Epilepsy has advanced the understanding of risk factors associated with SUDEP which   healthcare providers can use to talk to patients about epilepsy and SUDEP.
  • CURE Epilepsy also commemorates individuals who have passed away due to SUDEP. For example, CURE Epilepsy actively participates in an annual SUDEP Action Day in October, when families and organizations across the epilepsy community come together to raise awareness about SUDEP.  


Deep Dive

Sudden Unexpected Death in Epilepsy (SUDEP) refers to deaths in people with epilepsy not caused by drowning, injury, or other known causes of mortality. There is often evidence of an associated seizure, and the death is usually unwitnessed. Unfortunately, SUDEP is underrecognized and underestimated, as coroners and medical examiners may be unaware of the diagnostic criteria that define SUDEP.[1, 2] CURE Epilepsy has been the leading force driving research and raising awareness about SUDEP and since 2004 has funded over 40 projects totaling nearly $6 million to understand the basic biological mechanisms underlying this tragic outcome.   

Former CURE Epilepsy Board Director, Research Committee member, and SUDEP pioneer Jeanne Donalty has been a prominent voice in raising awareness of SUDEP and has worked tirelessly on grassroots approaches for awareness and prevention. Her work was motivated by the loss of her son Christopher when he was 21 years old, the recognition that healthcare providers rarely talked about SUDEP as a potential outcome of epilepsy, and the minimal research at the time in understanding SUDEP. Together with CURE Epilepsy, Jeanne worked with the National Institute of Neurological Disorders and Stroke (NINDS) to help create a “Center Without Walls” called the Center for SUDEP Research (CSR). The CSR employed a range of strategies to explore the causes of SUDEP and identify risk factors that may help prevent it. Former CURE Epilepsy Board Chair and volunteer Gardiner Lapham, who lost her son Henry to SUDEP, was instrumental in the formation of an organization called Partners Against Morality in Epilepsy (PAME). PAME continues to be a driving force in reducing epilepsy mortality by convening an annual conference of diverse stakeholders to discuss epilepsy mortality causes, share research discoveries, and identify means of prevention. CURE Epilepsy is a founding member of PAME and continues to be deeply involved by sitting on the Governance Committee, partnering on annual webinars, and financially sponsoring the annual meeting. 

In addition to advocacy and education, CURE Epilepsy funds innovative research in this field of study. Specifically, CURE Epilepsy researchers have developed SUDEP registries to get a more accurate understanding of the number of people affected, investigated risk factors for SUDEP, and studied the underlying biological mechanisms of SUDEP.   

Impact of SUDEP registries  

A registry is a database of people who have been diagnosed with a certain condition; it can be used to track the outcomes of participants and inform the care of other individuals with the same condition. Dr Elizabeth Donner at the University of Toronto was a recipient of CURE Epilepsy’s 2009 Sudden Unexpected Death in Epilepsy Award. With this funding, she developed a pediatric SUDEP registry in Canada to obtain data on every child with epilepsy who died suddenly and unexpectedly. While previous studies estimated that SUDEP affects 1 in 4,500 children with epilepsy each year,[3] Dr. Donner’s work estimated a much higher number: 1.11 cases of SUDEP per 1,000 children with epilepsy.[4] Her estimate is also in line with another study that made use of the Swedish National Death Registry.[5] Additionally, Dr. Donner and colleagues used the North American SUDEP Registry (NASR) and found that even those with well-controlled epilepsy may be at risk for sudden death.[6] Previous studies had suggested that SUDEP risk was highest in those with treatment-resistant epilepsy; however, the NASR study showed that sudden death can happen to anyone with epilepsy and that it should be discussed with everyone with epilepsy and their caregivers. Specifically, the study revealed that the risk of sudden death appeared to be higher in individuals who had not taken their most recent dose of antiseizure medication, those who were sleep-deprived, and those with psychiatric disorders.[6]  

Understanding the risk factors for SUDEP  

Dr. Torbjörn Tomson at the Karolinska Institute in Sweden was awarded a CURE Epilepsy grant in 2010, which was supported by the Leisher Family Award. His research involved a large, nationwide study on factors associated with increased risk of SUDEP; his findings confirm previous findings that generalized tonic-clonic seizures (GTCS) are a significant risk factor for SUDEP.[7] He found that individuals with GTCS living and sleeping alone are at significant risk for SUDEP. His work supports the use of seizure-monitoring devices to alert caregivers and the recommendation that people with GTCS should share a room with someone when sleeping whenever possible. Also, any treatments to reduce the occurrence of GTCS or to convert GTCS to non-GTCS could be useful in reducing SUDEP risk.[7] 

Understanding the genetic mechanisms underlying SUDEP    

CURE Epilepsy-funded grantees have investigated a multitude of targets and biological mechanisms in people affected by SUDEP, as well as in experimental animal models. The work of Dr. Annapurna Poduri and colleagues in Robert’s Program[1] at Boston Children’s Hospital explored common, underlying, genetic mechanisms that may be associated with SUDEP and other sudden unexpected pediatric deaths. Her team employed a “trio-based” approach, meaning that the child and their parents were studied to understand genetic changes that may have contribute to sudden unexpected death in these children.[8] Using this approach, many genes that were previously not associated with sudden death were reclassified; for example, genes such as SCN1A and DEPDC5 that are implicated in sudden pediatric death have also been shown to be relevant in SUDEP. Dr. Poduri also examined ten infants who died of sudden infant death syndrome (SIDS) and found that two children had variants of the SCN1A gene, which is also implicated in SUDEP.[9] Genes associated with cardiac issues such as arrhythmia and cardiomyopathy (a condition that makes it harder for the heart to pump blood) were also implicated in SUDEP.[8] In a separate study, CURE Epilepsy Award grantee Dr. Christopher Reid at the Florey Institute of Neuroscience & Mental Health at the University of Melbourne sought to understand the risk between SUDEP and cardiac arrhythmia (abnormal or irregular heartbeat). His team studied a gene called KCNH2, as mutations in this gene are linked to cardiac arrhythmias. His work demonstrated the role of KCNH2 mutations in SUDEP and suggests that genetic screening for KCNH2 could help understand an individual’s risk for SUDEP.[10, 11]

In addition to these and dozens of other scientific studies that CURE Epilepsy has funded and is currently funding on SUDEP, CURE Epilepsy is leading a project to standardize the data collected and reported in preclinical studies to improve transparency and rigor. Epilepsy researchers have an opportunity to comment on the common data elements (CDEs) developed through this project until December 31, 2023, after which CURE Epilepsy will distill and publish these best practices. Over the past 25 years, CURE Epilepsy has funded transformative science and significantly furthered awareness of SUDEP, and the organization will continue to prioritize this important area of research going forward in hopes of eventually preventing this tragic outcome.


Literature Cited:

  1. Sudden Unexpected Death in Epilepsy (SUDEP). Available at: https://www.cdc.gov/epilepsy/about/sudep/index.htm. Accessed October 5.
  2. Devinsky O. Sudden, unexpected death in epilepsy N Engl J Med. 2011 Nov 10;365:1801-1811.
  3. Harden C, Tomson T, Gloss D, Buchhalter J, Cross JH, Donner E, et al. Practice guideline summary: Sudden unexpected death in epilepsy incidence rates and risk factors: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the American Epilepsy Society Neurology. 2017 Apr 25;88:1674-1680.
  4. Keller AE, Whitney R, Li SA, Pollanen MS, Donner EJ. Incidence of sudden unexpected death in epilepsy in children is similar to adults Neurology. 2018 Jul 10;91:e107-e111.
  5. Sveinsson O, Andersson T, Carlsson S, Tomson T. The incidence of SUDEP: A nationwide population-based cohort study Neurology. 2017 Jul 11;89:170-177. 
  6. Chloe V, Fizza H, Elizabeth D, Brian DM, Jeffrey B, Dale H, et al. SUDEP in the North American SUDEP Registry Neurology. 2019;93:e227.
  7. Sveinsson O, Andersson T, Mattsson P, Carlsson S, Tomson T. Clinical risk factors in SUDEP: A nationwide population-based case-control study Neurology. 2020 Jan 28;94:e419-e429.
  8. Koh HY, Haghighi A, Keywan C, Alexandrescu S, Plews-Ogan E, Haas EA, et al. Genetic Determinants of Sudden Unexpected Death in Pediatrics Genet Med. 2022 Apr;24:839-850.
  9. Brownstein CA, Goldstein RD, Thompson CH, Haynes RL, Giles E, Sheidley B, et al. SCN1A variants associated with sudden infant death syndrome Epilepsia. 2018 Apr;59:e56-e62.
  10. Bleakley LE, Soh MS, Bagnall RD, Sadleir LG, Gooley S, Semsarian C, et al. Are Variants Causing Cardiac Arrhythmia Risk Factors in Sudden Unexpected Death in Epilepsy? Front Neurol. 2020;11:925.
  11. Soh MS, Bagnall RD, Bennett MF, Bleakley LE, Mohamed Syazwan ES, Phillips AM, et al. Loss-of-function variants in K(v) 11.1 cardiac channels as a biomarker for SUDEP Ann Clin Transl Neurol. 2021 Jul;8:1422-1432

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