Sudden Unexpected Death in Epilepsy (SUDEP)
Mortality due to epilepsy is a significant concern. Patients with epilepsy have a mortality rate significantly higher than that of the general population. The standardized mortality rate (SMR) is shown to be 1.6-9.3 times higher in this population.[1, 2, 3, 4, 5]
Epilepsy-related causes of death account for 40% of mortality in persons with epilepsy and include the following :
Death due to the underlying neurologic disorder in symptomatic epilepsy
Sudden unexpected death in epilepsy (SUDEP)
Accidents during an epileptic attack (ie, trauma, drowning, burning, choking)
Minimizing the risk of SUDEP
In the current absence of a proven SUDEP prevention method, the recommended approach is to attempt to keep modifiable contributory factors to a minimum.
As research indicates that SUDEP is largely a seizure-related phenomenon, optimization of seizure control is highly important. Recommendations to achieve this include:
- seeking regular medical consultation to re-evaluate epilepsy diagnosis, review medication and the possibility of new treatments, discuss implications of lifestyle changes etc;
- maintaining good adherence/compliance with the medication regime;
- identifying possible triggers for seizures and determining an effective strategy for keeping these to a minimum. For example, maintaining regular and adequate sleep patterns or learning ways to better manage stress.
It is also prudent for family, friends and caregivers to be informed of what to do during and following a seizure. This includes knowledge of the recovery position and cardiopulmonary resuscitation techniques. In addition, the necessity of calling an ambulance if the seizure lasts for more than 5 minutes or repeats without full recovery, and of staying with a person for 15-20 minutes after the seizure to ensure that recovery continues.
Although studies on SUDEP are heterogeneous in methodology and the accuracy of mortality data available, consistent patterns in incidence are obvious.SUDEP accounts for 8-17% of deaths in people with epilepsy.
In an attempt to standardize the definition of SUDEP, the US Food and Drug Administration (FDA) and Burroughs-Wellcome developed criteria for SUDEP in 1993. These criteria, now used in most SUDEP studies, are as follows:
The patient has epilepsy, which is defined as recurrent, unprovoked seizures
The patient died unexpectedly while in a reasonable state of health
The death occurred suddenly (ie, within minutes)
The death occurred during normal and benign circumstances
An obvious medical cause of death could not be determined at autopsy
The death was not the direct result of a seizure or Status epilepticus
Notably, evidence of a recent seizure does not exclude the diagnosis of SUDEP as long as death did not occur during the seizure.
Epilepsy related causes of death
SUDEP responsible for up to % of deaths
The FDA/Burroughs-Wellcome also defined the following categories:
Witnessed cases of SUDEP
Only a small portion of definite SUDEP cases have been documented as having been witnessed. Langen et al have reported 15 cases of witnessed SUDEP; 80% of these patients had a seizure immediately before death. Terrence reported 24% and Leetsma reported 38% of witnessed deaths to be an immediate consequence of a seizure attack. Kloster reported evidence of recent seizures (ie, witnessed, oral trauma, cyanosis) in 67% of victims.
However, in all witnessed deaths, seizures stopped before death, and in many cases, patients regained consciousness. In a few witnessed cases, the immediate event before death was a respiratory arrest (obstructive and central). Most victims were reported to have had difficulty breathing before death. Attempts at cardiopulmonary resuscitation were unsuccessful.
An ongoing study has documented SUDEP and has helped with understanding this phenomenon. The mortality in Epilepsy Monitoring Unit Study (MORTEMUS) is a collaborative project that aims to quantify the risk of death, SUDEP, and near-SUDEP in patients with drug-resistant partial epilepsy during long-term video EEG monitoring. One hundred forty-eight qualified eligible epilepsy centers participated in this study. Responses reflect an estimated total of 133,371 video EEGs and 2,814 patient-years of monitoring. Nineteen deaths were identified, of which 14 were determined to be definite or probable SUDEP. This study is ongoing and the final results are not yet published. A certain pattern has been established by observation in these patients. In most cases within 3 minutes after a seizure, a so-called shutdown of the EEG was noted, followed by asystole and, finally, apnea was the terminal phenomenon.
If SUDEP was shown to have occurred during sleep, a variety of circumstances might have contributed. A recent unwitnessed seizure with or without bradyarrhythmias and lack of sympathetic tone to oppose bradyarrhythmias might have contributed. In addition, obstruction of airways and asphyxia are more probable during sleep.
The interaction between the autonomic control of the cardiovascular functions and the seizure phenomenon is very complex.