Most people with epilepsy live a full and healthy life, and should not spend time worrying about potential epilepsy-related catastrophes. But people who live with epilepsy or with a loved one who has epilepsy should be aware that epilepsy occasionally can be fatal. This uncomfortable truth often is hidden or ignored because it is relatively rare and so hard to discuss. Some doctors argue: don’t inform patients, because it will be too frightening. Others, including the current author, think that doctors should provide factual information, and patients and families decide how they best can deal with the information. A recent survey (Vegni et al. 2010)among Italian epilepsy specialists showed that 62% discussed sudden unexplained death in epilepsy with very few of their patients and only 9% claimed to discuss it with all.
Overall, epilepsy increases the risk of dying by a factor ranging between 1.6 and 3 times that of the background population (Forsgren et al. 2005). How much does epilepsy shorten life, on the average? It depends upon the type of epilepsy. A study in the UK of 564 people with epilepsy followed for 15 years (Gaitatzis et al. 2004) showed that people with epilepsy of unknown cause died an average of two years earlier, but those with a known underlying serious disease causing the epilepsy died an average of 10 years earlier.
Death in association with epilepsy falls into five broad categories (Table 1). The first is “ordinary mortality” from the types of illnesses and traumas that everyone encounters. The second is death due to an underlying illness that causes epilepsy, such as stroke, cancer, genetic disorders or various other causes for epilepsy. This is the largest category. The third is death from co-morbidities, which are conditions that do not cause, but are associated with epilepsy, such as depression and suicide. The fourth is traumatic death from a seizure, for example, by crashing a car, falling down stairs, pneumonia after a seizure or drowning in a bathtub (see the safety section of this website here). The fifth category of mortality is SUDEP, sudden unexpected death in epilepsy, which is the focus of this section.
TABLE 1: TYPES OF CONDITIONS CAUSING INCREASED MORTALITY IN EPILEPSY
SUDEP, an abbreviation for sudden unexpected (some say “unexplained” but “unexpected” is the official term) death in epilepsy, is an almost self-explanatory term: it applies to a sudden death in someone known to have epilepsy, in the absence of an obvious cause for the death. Although most instances are presumed to occur during seizures, not all do and a seizure at the time of death is not a requirement for diagnosis of SUDEP. A widely accepted definition of SUDEP was proposed by Nashef in 1997: “the sudden, unexpected, witnessed or unwitnessed, non-traumatic, and non-drowning death of patients with epilepsy with or without evidence of a seizure, excluding documented status epilepticus, and in whom post-mortem examination does not reveal a structural or toxicological cause for death.”
SUDEP has been subcategorized as definite, probable and possible. Definite SUDEP meets the general definition above, including information from an autopsy to rule out other causes of death. Probable SUDEP meets the definition, but in the absence of an autopsy. Possible SUDEP refers to instances of sudden death in a person with epilepsy with no clear cause, but plausible explanations other than SUDEP
The number of people dying from SUDEP is difficult to determine. There is no central national or regional registry with long-term follow-up data to track such deaths, although several are being formed, particularly in Europe, Canada and the United States. Information from county and state mortality registries is incomplete and incorrect. Mortality statistics are based largely on diagnoses written on death certificates by treating physicians. Many physicians are unfamiliar with SUDEP, and so would not list SUDEP on a death certificate. County Medical Examiners, who often sign off on cases of otherwise unexplained or suspicious deaths, are more likely to have heard of SUDEP. Still, their diagnosis might make no mention of SUDEP, referring only to “epilepsy” or “seizure.”
Incidence means number of new cases per population per year. The incidence of SUDEP ranges in different studies from 0.9 – 93 cases per 10,000 people per year (Tomson et al. 2008). This large variability depends upon study methods, but also on the population being studied. In a large community population where the majority of epilepsy is controlled, SUDEP rates are in the range of 10-30 SUDEP cases per year among 10,000 people with epilepsy. Mortality is much higher among those with uncontrolled epilepsy serious enough for them to be considered to be candidates for epilepsy surgery, ranging from 63-93 SUDEP cases per 10,000 people each year.
SUDEP has been estimated to account for 15-20% of all cases of death in people with epilepsy (Pedley and Hauser 2002). SUDEP is more likely in people with uncontrolled tonic-clonic (grand mal) seizures, those who are having seizures but not taking adequate doses of antiepileptic medications. Those who take multiple antiepileptic drugs are at higher risk, but this may be because many who are taking multiple medications are having more frequent or more severe seizures, and that is the real risk factor. Seizures that occur during sleep may increase the risk. Males and African-Americans may be higher risk. Many other risk factors have been considered, but not yet proven. Among people with uncontrolled epilepsy, SUDEP is not rare, emphasizing the urgent need for better diagnosis, prevention and treatment of uncontrolled epilepsy.
The cause of SUDEP is not entirely known, although there are several plausible theories. No ethical investigator would intentionally subject people with epilepsy to the types of stresses that might produce SUDEP for purposes of study. Laboratory models of SUDEP exist, but there always is uncertainty about whether they faithfully represent the real disease. Most theories about SUDEP focus on breathing (respiration), heart rhythms and brain function.
A pause in breathing, called apnea, is common during or after a seizure. Studies during video-EEG monitoring (O’Regan and Brown 2005) have shown breathing pauses longer than 15 seconds in 30% of partial seizures. Such pauses can be associated with significant drops in blood oxygen levels (Blum et al. 2000). Normal oxygen saturation in blood is above 98%, and significant problems can occur with saturations less than about 85% in people unaccustomed to such low oxygen blood levels. A study monitoring oxygen levels during seizures (Bateman and Seyal 2009) showed oxygen levels below 90% in 33% of seizures, below 80% in 10% of seizures and below 70% in 4% of seizures.
Apnea can be caused by obstruction in the pharynx or throat blocking air passages, or by loss of breathing signals normally directed by the brainstem to the respiratory muscles. Brain failure of breathing signals is called central apnea, and it seems to be the type of apnea seen during seizures. However, some authors have argued that post-seizure apnea can also be from throat obstruction.
Autopsies after SUDEP and laboratory experiments in models of SUDEP sometimes show lung tissue filled with water, a condition called pulmonary edema. The water component of blood leaks from lung capillaries into lung tissue, because the capillary fluid is under high pressure. During seizures, this high capillary pressure results from seizure-induced constriction of the veins draining blood from the lungs. With water in the lung tissue, blood oxygenation drops. Pulmonary edema can add to the oxygenation problems produced by apnea. A few published cases have documented prolonged apnea in conjunction with SUDEP.
How often apnea is the mechanism for SUDEP cannot be known. At what point in a seizure-related respiratory pause would it make sense to give oxygen or artificial respiration? The answers are not known. Standard seizure precautions for a patient hospitalized with seizures include delivery of oxygen by mask or nasal prongs during and after a seizure. Yet, oxygen therapy rarely is prescribed for home use. The reason for this discrepancy is unknown.
Heart rhythm problems likely account for some instance of SUDEP. During seizures, changes in heart rate are common, the usual change being an increase of heart rate during a seizure, but other serious arrhythmias can occur (Nei et al. 2000). More serious are very high rates that interfere with the heart filling with blood, or pauses in the heart rate.
An electrocardiogram can measure the electrical pattern of the heartbeat and display it on a chart or screen. The components of the heart’s electrical discharged are labeled with letters: P, Q, R, S and T. The interval of time between the Q and the T waves is called the QT interval. QT intervals that are either too short or too long are associated with increased risk for irregular heartbeats. In 2009, Baylor Medical College investigators in Houston (Goldman et al. 2009) discovered that mutations in a gene called KCNQ1 predisposed laboratory animals to have a long QT interval and seizures. This raised the possibility that the KCNQ1 gene could be involved in some cases of SUDEP, and also that an EKG might be a good screening test for a long QT interval as a risk factor for SUDEP.
A review of three series of EEG (brainwave) and EKG (heart rhythm) monitored cases showed that 2.7–4.0 per 1000 patients had at least one episode of a significant heart pause during a seizure (Tomson et al. 2008). But inpatient video-EEG monitoring takes place in a hospital over only a few days. What happens with heart rhythms in real life? In 2004, the prestigious journal, Lancet, published a study (Rugg-Gunn 2004) of 20 patients with epilepsy, whose heart rhythm was monitored continuously for 24 months with an implanted recording device. Most seizures did not produce dangerous cardiac rhythm problems, but 3 patients (15%) showed a cardiac pause lasting at least 5 seconds during a seizure. Seizure-induced heart rhythm problems might reduce blood flow to vital organs and lead to death in some cases of SUDEP. However, this is speculative. Several cases of “near-SUDEP” have been recorded during EEG and heart monitoring. Some have shown concurrent cardiac arrhythmias, but others had normal heartbeats for long after the brainwaves had flattened, suggesting that for those cases the heart was not the problem.
Brain dysfunction is another category of possible causes for SUDEP. Blood flow to brain increases markedly during a seizure to keep up with the demands of the increased electrical activity. The increased brain blood flow raises pressure inside the closed head. If the pressure becomes too high, then brain tissue can be compressed and injured, resulting in a stroke-like picture or possibly even death. This is extremely rare. Short of compression, seizures might cause the vital centers in the brainstem that control blood pressure and respiration to temporarily malfunction.
Mixed causes: SUDEP probably results from a variety of causes, related to problems with heartbeat, breathing and brain function. Different people may have different causes and more research will be needed to clarify the most important causes.
Patients, families and doctors who know about SUDEP may sometimes be able to prevent it. The first step is to strive for the best possible seizure control, since most cases of SUDEP are associated with a seizure. Taking seizure medications regularly may avoid a low blood level of medicines and a resulting breakthrough seizure (see section on medication compliance). Some studies suggest that, where appropriate, epilepsy surgery to cure or ameliorate seizures might prolong life. Several companies are working on seizure monitors to notify family when a seizure is beginning. An implantable device is being tested to provide a warning of a seizure that is about to happen - a seizure predictor. Several monitoring devices can be found by searching the web with the terms “seizure monitor,” but we do not endorse any particular product (disclosure: the author consults for companies developing seizure notification and seizure prediction devices). Monitors for breathing and heartbeat also are under development and testing. Until these devices become validated and widely available, a simple intercom or baby monitor may provide notification of a seizure. None of these monitors, however, will prevent seizures. If a child or adult is not breathing after a seizure for more than 10 seconds, knowing how to give artificial respiration can be lifesaving. It is uncertain whether delivery of oxygen after a seizure by mask or nose prongs would reduce risk of SUDEP, but oxygen is probably harmless for those who do not have lung disease such as emphysema and are not newborns. Turning a person from the prone (face down) to the supine (face up) position has been hypothesized to reduce SUDEP and the chance of suffocation during a seizure, but firm evidence for this is lacking.
Researchers are trying to find medicines, other than antiepileptic drugs, that will reduce the risk for SUDEP. None of these are ready for use outside of a supervised experimental trial. Some drugs may stabilize heart rhythm. Others, for example the antidepressant paroxetine (Paxil) can stimulate breathing in some situations (Kraiczi et al. 1999). A trial of omega-3-fatty acids, found in fish oils, is being undertaken to evaluate protection against SUDEP (http://clinicaltrials.gov/ct2/show/NCT00871377?term=omega+3+and+SUDEP&rank=1) Research on SUDEP will provide better clues to its genetic and environmental causes, prevalence and possible treatments. It must be said however, that SUDEP is still largely unpreventable, and those who have a family member with SUDEP should not feel that they could have prevented it.
TABLE 2: POSSIBLE PREVENTIONS FOR SUDEP
Information on epilepsy and SUDEP can be found at www.epilepsy.com and at the Epilepsy Foundation site. The Epilepsy Therapy Project encourages application for research funding for new epilepsy therapies, including prevention of SUDEP. The CURE Foundation (Citizens United Against Epilepsy, www.cureepilepsy.org) has committed to substantial support for research on SUDEP. Additional research support has been provided by the American Epilepsy Society, the Epilepsy Foundation, FACES at NYU and the NIH. Several support groups are available for those concerned about SUDEP, and these groups also sometimes fund research projects. Such sites include Epilepsy Bereaved, SUDEP Aware and www.dannydid.org/sudep.
The American Epilepsy Society, an organization of professionals working in the epilepsy field, has formed a “Special Interest Group” on SUDEP which will meet annually. A task force published a summary of the needs in Epilepsia. 2009 Apr;50(4):917-22 , with an abstract accessible at http://www.ncbi.nlm.nih.gov/pubmed/19054406 .
Epilepsy.com has information relevant to SUDEP at several sites, including:
Ultimately, progress will happen because different elements of the medical community come together to increase research, available accurate information and public awareness. SUDEP coalitions are being formed to accomplish these goals. The Epilepsy Therapy Project is expanding its focus on SUDEP in three ways. First, it will provide more content on SUDEP on its website. Second, it will expand awards for grants for innovative therapies to prevent SUDEP. Third, it will cooperate with other epilepsy groups to support SUDEP initiatives and awareness.
Please note: As a website, we cannot provide medical advice, diagnoses or respond personally to emails. We do, however, have interactive forums that encourage exchange of information about epilepsy.
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