SUDEP: Sudden Unexplained Death in Epilepsy
Elizabeth J. Donner, MD
"The danger to life of patients with epilepsy is not great."
Gowers, 1885
Mortality in Epilepsy
It has long been accepted that epilepsy is not a fatal condition and this opinion remains widely held by heath professionals today. However, it has been established that people with epilepsy carry an increased risk of death when compared to the general population. Researchers have tried to quantify the risk of death by examining rates and causes of death in populations of people with epilepsy. Cockerell and his colleagues followed 564 patients with 'definite epilepsy' in the United Kingdom for 6.9 years. They found that their subjects had a 3 times increased rate of death when compared to the general population. This figure generally agrees with previous reports of 2 to 3.5 times increased risk of death in people with epilepsy.
This increased mortality has been largely attributed to the disease underlying the epilepsy. Some conditions, such as brain tumors and neurodegenerative diseases, cause seizures and are associated with premature death. Deaths may also be due to epilepsy itself, such as an accident or drowning during a seizure. Included in the category of deaths due to epilepsy is a phenomenon known as Sudden Unexplained Death in Epilepsy (SUDEP).
SUDEP refers to people who have epilepsy and die suddenly and unexpectedly, and no cause of death can be found. An autopsy must be done to confirm this diagnosis. Autopsy reports in SUDEP often list the cause of death as seizure or epilepsy. Although there may be physical or circumstantial evidence of a seizure having occurred, we know that seizures themselves are rarely fatal. Complications from a seizure, including choking and suffocation may cause death, and in these circumstances the proper cause of death is documented on autopsy. In SUDEP, the cause of death remains elusive.
Incidence of SUDEP
The incidence of SUDEP in adults with epilepsy has been studied by several investigators. Tennis and her colleagues identified from the Saskatchewan Health prescription drug file 3,688 adults, aged 15 to 49 years, taking anticonvulsants. They found the incidence of sudden unexplained death in this group to be approximately 1 death per 1,000 people with epilepsy per year. As anticonvulsants may be used to treat other conditions besides epilepsy, this study may have included people being treated with anticonvulsants but not necessarily with diagnosed epilepsy. Ficker and his colleagues studied 1,535 people with epilepsy in Rochester, Minnesota between 1935 and 1994. They found the incidence of SUDEP to be 0.35 per 1,000 person years.
There have also been studies of sudden death in the general population. For the sake of comparison, Hauser and his group found the incidence of sudden death in the general population of adults less than 45 years of age in Rochester, Minnesota from 1934 to 1985 to be 5 to 10 per 100,000 people per year. This suggests that the rate of SUDEP is at least 10 times that in the general population.
Risk Factors for SUDEP
By studying cases of SUDEP, researchers have identified certain groups at higher risk. Leestma and his group conducted a prospective study identifying all sudden deaths in patients with epilepsy over one year in Chicago. This is the largest study, containing 60 patients. They found male gender, a history of alcohol abuse, and low blood anticonvulsant levels to be risk factors for SUDEP. Earnest and colleagues studied 39 adult cases of SUDEP and reported that 92% had blood anticonvulsant levels below the recommended range. George and Davis reviewed 52 cases of sudden unexplained deaths in people with epilepsy and found 69% had low blood anticonvulsant levels compared with 34% of a control population. These studies support the association between low anticonvulsant blood levels and SUDEP.
Other smaller studies have been conducted in select populations of people with epilepsy and have found higher incidences of sudden unexplained death in people with refractory epilepsy, defined as requiring 2 or more anticonvulsants, in people with severe epilepsy and learning difficulties enrolled in a residential school and in patients enrolled in an epilepsy surgery program. These studies do seem to support the finding that epilepsy severity is related to an increased incidence of SUDEP.
Working Towards a Better Understanding of SUDEP
The goal of SUDEP research is to determine the underlying cause of this phenomenon. The identification of risk factors such as more severe epilepsy and low blood anticonvulsant levels suggest that seizures play a role in these sudden unexpected deaths. Despite this, SUDEP does not always occur during or after a seizure. Although in many cases of SUDEP the deceased are found dead in bed, making it impossible to confirm if a seizure occurred, there are cases of witnessed SUDEP with no preceding seizure.
Sudden unexpected death in people without epilepsy is usually cardiac in origin which suggests that the heart may play a role in SUDEP as well. To date there is very little research to support that people with epilepsy are at an increased risk of sudden cardiac death. It may be that the answer lies in the complex connections between the brain and the heart. These are the areas that further research must explore.
Elizabeth J. Donner, MD, a resident in Paediatric Neurology at the University of Toronto and the Hospital for Sick Children in Toronto, is currently conducting a study of Sudden Unexplained Death in Children with Epilepsy.
