Epilepsy is a common neurological disorder associated with significant morbidity and a high mortality rate. The fourth most common neurological condition in the world, epilepsy, is characterized by abnormal neuronal activity resulting in seizures which have diverse clinical presentations, as well as widespread neuronal loss and pathological deficits in the brain. Despite the prevalence of epilepsy around the world, very few people are aware of the range of devastating impacts that epilepsy can potentially have on a patient, and sudden unexpected death in epilepsy (SUDEP) is one of the most important but least known of these possible worrying results. In 1997, SUDEP was defined as “sudden, unexpected, witnessed or unwitnessed, nontraumatic and non-drowning death in patients with epilepsy, with or without evidence for a seizure and excluding documented status epilepticus, in which postmortem examination does not reveal a toxicologic or anatomic cause of death” , and although this formal definition has changed in recent years, it has remained relatively consistent.
What Is SUDEP?
Currently, SUDEP, or sudden unexpected death in epilepsy, is the leading cause of epilepsy-related death, and patients with epilepsy are 24 to 27 times more likely to experience sudden death, with drug-resistant patients having been proven to be even more likely to die from SUDEP . However, despite the overall prevalence of SUDEP, its cases are currently considered to be highly unrecognized and underreported. This is because 90% of cases are unwitnessed, therefore critical information regarding the events leading to death are not known. This leaves the medical history and postmortem findings as the only source of information, and these often prove insufficient to accurately pinpoint the cause of death. Death certificates highly underestimate the SUDEP in epilepsy, attributing 1.5% of sudden deaths to seizure complications and seizures themselves . When the patient undergoes autopsy, pathologists performing the autopsy tend to ignore SUDEP cases based on the rather vague pathological findings . Another pitfall would be the existence of conditions such as a minor coronary artery disease in patients because death could be falsely attributed to these conditions instead of SUDEP. Therefore, better standardization of the pathological criteria, raised SUDEP awareness and better documentation are essential in the pursuit to understand and prevent SUDEP.
Understanding the Biological Mechanism Behind SUDEP
Despite vigorous efforts, the pathophysiology of SUDEP remains obscure, however there have been numerous possible SUDEP mechanisms which have been proposed by a variety of different studies. For example, the 2013 MORTEMUS study, which studied 16 different SUDEP patients, was a milestone in SUDEP research. This study allowed scientists to better understand the mechanism underlying SUDEP and concluded that in the cases examined, a generalised epileptic seizure led to early alteration of respiratory and cardiac function. This led either to immediate death or to a period of restored cardiorespiratory function before cardiac arrest occurred . Furthermore, a variety of SUDEP studies have observed that the majority of SUDEP cases occur at night . This may suggest that circadian rhythm plays a role in SUDEP.
Genetic Variants Contributing to SUDEP
SUDEP has also been shown to potentially be linked to various genes. In a study, 61 people with SUDEP were genetically tested, and it was shown that four had mutations in the same four genes. A further nine had variants in candidate genes for cardiac arrhythmia, a disorder which is thought to accompany SUDEP . Overall, various studies each propose different possible mechanisms for SUDEP, indicating that the condition could be attributed to a variety of possible factors in epileptic patients.
Lack of Awareness
In addition to obscurity surrounding the specific biological mechanism behind SUDEP, there is little to no awareness about the condition. In fact, the concept of SUDEP only gained recognition in the 1990s. Until then, there was almost no public awareness of its potential impact on people with epilepsy and very little in the medical literature. In 1995, the charity Epilepsy Bereaved was founded by families who had been affected by SUDEP in order to raise awareness amongst the public and medical community. The first international conference was held in 1996 which led to the first international publication on SUDEP . Following the landmark paper by Nashef which standardised the definition of SUDEP , research into SUDEP gained huge momentum.
Increased awareness of SUDEP amongst the medical community has been vital in ensuring that cases of possible SUDEP are referred to the coroner for investigation. All cases are now highly encouraged to receive a SUDEP autopsy in order to exclude other causes of death. There have been many reports of likely SUDEP cases being issued another cause of death, such as status epilepticus, or accidental death by medical professionals and coroners despite there being no evidence for this. SUDEP may therefore be underreported and the inaccurate classification of these deaths may skew studies aiming to identify relevant risk factors.
In addition to this overall misdiagnosis of SUDEP cases, the discussion of SUDEP with patients and their caregivers has always been a controversial topic. The National Institute for Health and Care Excellence updated their guidelines on epilepsy management in 2004 to include SUDEP . They advise that giving patients tailored information about their risk of SUDEP should be done as part of a counselling checklist for patients with epilepsy and their families. The most common reasons given for not discussing SUDEP are that neurologists feel that their patients are at low risk and they fear a negative reaction. In fact, some doctors have even suggested that to disclose the risk of SUDEP when not sought by the patient may in fact be unethical as there is no proven intervention to minimise SUDEP and that knowledge of the condition may negatively impact quality of life. It was also reported that doctors are unlikely to be found negligent for not discussing SUDEP as there is no proven preventative measures or intervention . On the flip side, the most common reasons given for discussing SUDEP were the patients inquiring about it themselves and the neurologist counselling someone with known SUDEP risk factors. However, there is mounting evidence that patients and their families wish to be informed of the risk of SUDEP . Furthermore, despite not routinely being informed of the risk does not mean that patients are ignorant of SUDEP and they may resort to inaccurate and unreliable sources that do not take into account their personal risk of SUDEP, making it imperative that doctors address the issue.
Partially due to a lack of understanding about SUDEP and a lack of overall awareness both by the public and medical community, there remains no effective evidence-based preventions against SUDEP. Strategies to try to prevent SUDEP include reducing the number of seizures a patient has (by considering epilepsy surgery or making lifestyle changes), examining for heart and breathing problems during and following seizures, and supervising patients at night or using safety pillows to prevent breathing difficulties. Furthermore, the use of a safety checklist has gained interest since it was first proposed and has subsequently been developed into a smart-phone app . In addition, drugs that increase the brain chemical serotonin and reduce the brain chemicals adenosine and opioids have also been recently proposed as future targets for SUDEP prevention but there have been no trials examining the benefits of these in the prevention of SUDEP.
Within the hospital setting, several interventions are also recommended to reduce the duration of seizures, respiratory dysfunction and EEG suppression,which are all thought to contribute to SUDEP. These include repositioning of the patient during a seizure, oral suctioning and oxygen administration. The MORTEMUS study also showed that in near-SUDEP cases, where patients almost died from SUDEP but ended up surviving, resuscitation was prompt whereas in the SUDEP cases it was delayed suggesting that close monitoring of patients in hospitals with the use of direct supervision, ECG, EEG and oxygen may reduce the risk of SUDEP significantly .
Despite all these efforts, there remains no consistently proven preventative strategy for SUDEP, although several of those described show promise and deserve further research to determine their effectiveness. Furthermore, many neurologists fail to mention the risk of SUDEP to epilepsy patients, reminiscent of when doctors and families would not tell people they had cancer. But today, patients learn not just about cancer but about many other potentially fatal conditions. So the quiet about the epilepsy death risk appears to be an anomaly. This is due to a variety of different factors including an overall lack of awareness, lack of understanding, and lack of diagnosis or recognition of SUDEP cases. Overall, more attention needs to be brought to the prevalence of SUDEP among epileptic patients in order to more effectively diagnose, research, and understand SUDEP, and ultimately mitigate the risks of the condition.
Lori is currently a junior at Horace Greeley High School in Chappaqua, NY, and is the president of the Westchester chapter of the IYNA. A competitor at the USA National Brain Bee in 2019 and a student who has been actively involved in neuroscience research since her sophomore year in high school, she has a large interest in neuroscience and is dedicated to furthering the overall goals of the IYNA and teaching students about the final frontier: the human brain!