SUDEP

(Sudden Unexplained Death in Epilepsy)
In Memory of Katherine (Katie) Baldwin Goldman
(1974-2006)


BACKGROUND
It is acknowledged that the majority of patients with epilepsy lead full and healthy lives.
However, it has been recognized that a small population of patients with epilepsy may die suddenly and without warning. Although a rare occurrence, unexplained and unexpected death in persons with epilepsy does occur.


The term SUDEP has been coined to reflect sudden death in persons with a diagnosis of epilepsy for whom there is no obvious cause of death. You may find the acronym SUDEP defined as sudden unexplained or unexpected or just sudden death in epilepsy. The following is a definition of SUDEP found in the epilepsy literature: "Sudden, unexpected, witnessed or unwitnessed nontraumatic and nondrowning death in an individual with epilepsy, with or without evidence for a seizure and excluding documented status epilepticus where postmortem (autopsy) does not reveal a toxicologic or anatomic cause for death." (Nashef) Cases that fulfill most of these criteria may be designated "probable" or "possible".


Difficulty in determining how often SUDEP occurs is affected by lack of consensus in the definition, and lack of acknowledgement of SUDEP by coroners and medical examiners. Additionally SUDEP occurrence varies based on the populations studied. In patients with chronic epilepsy the incidence is 1-2 persons per 1000 persons per year. The highest rate is in patients with severe refractory seizures and is 3-9 persons per 1000 persons per year. (Tomson)


WHY HAVE I NEVER HEARD OF SUDEP?
You may acknowledge that your health care provider (HCP) has never mentioned SUDEP. . As a person with epilepsy or a family member giving care to someone with epilepsy, it is important to know about SUDEP. One reason that you may have never heard of it is that there has been controversy in the epilepsy community regarding how and when SUDEP should be discussed. Some HCP feel that bringing up SUDEP may produce fear or undue anxiety. Also, for individuals with certain types of seizures (e.g. absence or myoclonic), or those with well controlled seizures, there is no known increased risk for SUDEP. Additionally, it may not be discussed because although SUDEP has been studied and researched by the epilepsy community for more than 20 years, how and why it occurs and methods to prevent it are still largely unknown. However, the Epilepsy Foundation of Georgia believes that SUDEP information should be part of a comprehensive education program (provided by the patient's neurologist or epileptologist), to patients with a known diagnosis of epilepsy.


ARE ALL PERSONS WITH EPILEPSY AT RISK FOR SUDEP?
No. Studies have shown that some individuals may be at higher risk than others for SUDEP. Recent research indicates that the highest risk for SUDEP is in those patients who have uncontrolled generalized tonic-clonic seizures (especially those occurring during sleep), followed by those who are on three or more antiepileptic drug at the same time. Of course, this is just identifying a subpopulation of patients with very difficult to control epilepsy, and is not implying that using more than two antiepileptic drugs is the cause of SUDEP.


Additionally, those adults who have had epilepsy since infancy or childhood have a higher risk for SUDEP, as are individuals (male and female) in the 20-40 year range. SUDEP may also occur in children, with the range of reported cases from 8 months to 83 years of age. (Tomson)


Other risk factors include noncompliance with antiepileptic medications, which in one study was found to be associated with an over three times increased risk of mortality in patients with epilepsy. (Faught)


WHAT CAUSES SUDEP?
The cause is not known. Researchers have looked at: age, genetics, cardiac abnormalities, autonomic dysfunction, respiratory mechanisms, the role of seizure medications, neurotransmitters (brain chemicals), mechanisms of sleep (as SUDEP often occurs during sleep), prone position in sleeping (many deceased are found face down), and others.


Much of the research regarding SUDEP has been in looking at cardiac rhythm abnormalities in patients with epilepsy. Some patients with generalized tonic clonic seizures are noted to have ictal (during seizure) and resting tachycardia (fast heart rate), while others have bradyarrhythmias (very slow and irregular heart rate). There may be a role for EKG evaluation in patients with very hard to control epilepsy, looking for abnormalities such as acquired prolonged or shortened QT syndrome. However, much more research is needed in this area before a consensus opinion regarding EKG monitoring or cardiac interventions are recommended.


Some encouraging research into the area of ion channel dysfunction (Goldman) may shed some light on both epilepsy and SUDEP, as some epilepsy syndromes are caused by ion channel dysfunction. The SCN5A gene coding for a sodium channel and the KCNA family of potassium channel genes may be expressed in both brain and heart tissue. In time this information may guide treatment options to improve seizure control and reduce the risk of SUDEP. Genetic screening may become a standard part of epilepsy care much as the EEG and MRI are today.


SUDEP probably results from a variety of causes related to problems with heartbeat, breathing and the source of an individual's epilepsy. Certainly much more research in this area is needed.


WHAT CAN BE DONE TO DECREASE THE RISK OF SUDEP?


THE FOLLOWING ARE POSSIBLE AIDS TO CONSIDER:


In addition, knowledge of emergency resuscitation measures including first aid for seizures, when to call 911, and cardiopulmonary resuscitation (CPR) are important for all when a member of the family has epilepsy. Information regarding first aid for seizures is available through the Epilepsy Foundation of Georgia; CPR classes are available through the American Heart Association or the American Red Cross.


AFTER SUDEP, WHAT?
When SUDEP does occur, families often experience significant grief and have many questions. Many are angry because they have never heard of SUDEP. They may question what they could have done to prevent it, and may feel guilt over a variety of issues associated with their loved one's death. They should be given the opportunity to talk with the patient's HCP to have questions answered. They also may need to be referred for counseling. Mental health workers dealing with sudden death and grief may be especially helpful.


Dr. Elizabeth Donner, a pediatric neurologist at the Hospital for Sick Children in Toronto, Canada, and leading expert on SUDEP states, "Increasing awareness is the first critical step to improving our understanding of this devastating condition. From knowledge comes the potential for life-saving action."


RESOURCES

The Epilepsy Foundation of America
www.epilepsyfoundation.org/about/SUDEP

Danny Did Foundation www.dannydid.org
Founded in 2010 by the parents of Danny, a four year old who died in 2009 due to his epilepsy. Their goals are to advance awareness of SUDEP, enhance communication about SUDEP between healthcare professionals and persons with epilepsy, and provide information about technological advances in seizure detection and prediction devices.

SUDEP Aware www.sudepaware.org/index.html
This is a not for profit organization founded in 2008. They are based in Toronto, Canada. Their goals are to promote knowledge and understanding of SUDEP through: education of lay and professional communities, accurate identification of SUDEP deaths, and encouraging research to understand SUDEP. This website carries a list of current research in SUDEP.

epilepsy.com www.epilepsy.com/epilepsy/sudep_intro

Epilepsy Bereaved (United Kingdom) www.sudep.org
Founded in 1993, Epilepsy Bereaved is the leading voluntary organization working internationally to prevent unnecessary deaths from SUDEP.

Citizens United Against Epilepsy www.cureepilepsy.org


REFERENCES

Donner, E. (2011) "Explaining the Unexplained: Expecting the Unexpected: Where are we with Sudden Unexpected Death in Epilepsy.' Epilepsy Currents 11 (2): 45-49.

Faught, E. Duh, MS et al (2008) "Nonadherence to antiepileptic drugs and increased mortality. Neurology 71: 1572-1578.

Nashef, L. (1997) "Sudden Unexpected Death in Epilepsy: Terminology and Definition" Epilepsia 38 (Suppl 11): 56-58.

Goldman, AM Glasscock E., Yoo JW, Chen TT, Klassen Tl, Nlebels JL ((2009) Arrhythmia in heart and brain: KCNQ1 mutations link epilepsy and sudden unexplained death. Sci Transl Med 1: 1-9.

Tomson, T., Walczak, T et al (2005) "Sudden Unexpected Death in Epilepsy: A Review of Incidence and Risk Factors" Epilepsia 46 (Suppl 11): 54-61.