Sudden Unexpected Deaths in Epilepsy

[Media interested in covering this research: click here to view the media release or call Tanya Sarina on 0431 029 215]

Sudden unexpected death in epilepsy (SUDEP) is the most common cause of epilepsy-related death and responsible for about 150 Australian deaths each year (1) yet the underlying cause has remained a mystery. New findings from the Centenary Institute have revealed faulty heart genes may be the missing link, according to research published today in Brain Pathology.

SUDEP is the term applied to sudden death occurring in a person with epilepsy for no apparent reason. When such a death occurs and all other possible causes of death are excluded, SUDEP is usually attributed as the cause of death. (2)

"Sudden unexpected death in epilepsy occurs mainly in young people so these findings could have a huge impact in saving lives through early diagnosis. The ultimate goal will be to use genetic screening of patients with epilepsy to identify these gene mutations that could increase the risk of sudden unexpected death," said lead author Centenary Institute and University of Sydney Head of Molecular Cardiology Professor Chris Semsarian.

The research of people with epilepsy who had died from a sudden unexpected death discovered the presence of certain genetic mutations found in a potentially fatal heart disorder known as long QT syndrome. Long QT syndrome is caused by mutations in more than 10 genes and eight of these can interfere with the ion channel of cell membranes and disrupt their ability to regulate electrical activity in our body. This disruption of the ion channels can lead to abnormal, life-threatening heart rhythms.

The link was discovered by the researchers who checked the post-mortem blood samples of cases of sudden unexpected death in epilepsy from 1993 to 2009 for the three most common long QT syndrome genes (KCNQ1, KCNH2 (HERG), SCN5A). Of the 48 cases that could be analysed, the researchers found the faulty genes were present in six (13%) cases.

While the findings are a major first step in understanding the cause of sudden unexpected death in epilepsy, more research is needed to determine the exact role these genetic mutations play.

Professor Semsarian said: "These findings clearly demonstrate genetic mutations that disrupt the ion channels play a role in sudden death in people with epilepsy. However, we were unable to review medical histories to look at a family history of sudden death, epilepsy and/or long QT syndrome so it remains to be determined whether these changes are the genetic cause or an accompanying risk factor."

About Sudden Unexpected Death in Epilepsy (SUDEP)

Epilepsy Australia has provided the Centenary Institute with the following information on sudden unexpected death in epilepsy (SUDEP):

"Epilepsy is a common neurological condition in which a person has a tendency to have recurring seizures. Good seizure management is essential to reduce the risks associated with epilepsy. A seizure is not usually dangerous, but a person is at risk if they are in a dangerous environment and they have impaired awareness, or they are unconscious.

"Death related to epilepsy is rare, but it can occur. Sometimes it is directly related to unremitting seizures, as in the case of status epilepticus. However, sudden unexpected death in epilepsy (SUDEP) can also occur and the reasons for this are not yet understood. Studies of SUDEP suggest that the risks are particularly low in those who have infrequent seizures. Therefore it is important for people with epilepsy to aim for excellent seizure control. A thorough evaluation of new onset seizures is essential, followed by careful adherence to the recommended medical treatment plan. Regular medical reviews will ensure that the best possible seizure control is maintained over time."

For more information visit the Epilepsy Australia website or call 1300 852 853.

For more information about research into sudden cardiac death at the Centenary Institute Agnes Ginges Centre for Molecular Cardiology, please click here or call (02) 9565 6187.

References

1. Australian Institute of Health Welfare. Annex Table 2: Deaths by cause, sex and mortality stratum in WHO regions, estimates for 2002. World health report [document on internet]. Canberra: AIHW, 2004 [cited 2009 Jun 1].
2. Black M. SUDEP and the post mortem. In Chapman D, Moss B, Panelli R, Pollard R, eds. Sudden unexpected death in epilepsy: a global conversation. Camberwell: Epilepsy Australia & Epilepsy Bereaved, 2005;20-21.

Media only: please contact Centenary Institute Communications Manager Tanya Sarina on 02 9565 6228, mob: 0431 029 215 or email: